INVESTIGADORES
KATZ Eleonora
congresos y reuniones científicas
Título:
Ryanodine is a positive modulator of acetylcholine gating in cochlear hair cells
Autor/es:
ZORRILLA DE SAN MARTIN, J; BALLESTERO, J; KATZ, E; ELGOYHEN, AB; FUCHS, PA
Lugar:
Denver, USA
Reunión:
Congreso; 30th Midwinter Meeting, Association for Research in Otolaryngology; 2007
Institución organizadora:
Associtation for Research in Otolaryngology
Resumen:
The efferent synaptic specialization of hair cells includes a near-membrane synaptic cistern whose presence
suggests a role for internal calcium stores in cholinergic inhibition. Calcium release channels from internal stores
include ryanodine receptors whose participation is usually demonstrated by sensitivity to the eponymous plant
alkaloid, ryanodine. However, use of this and other store-active compounds on hair cells is confounded by
the unusual pharmacology of the á9á10-containing hair cell nicotinic cholinergic receptor (nAChR), which has
been shown to be antagonized by a broad spectrum of compounds. Surprisingly, we found that ryanodine is a
positive modulator of the a9a10 nAChR expressed in Xenopus oocytes, the first such compound to be found
and corresponds to an increase in the apparent affinity and efficacy for acetylcholine (ACh). Moreover, AChevoked
currents through the isolated cholinergic receptor of inner hair cells (IHCs) in excised mouse cochleas were
enhanced ~ 50% by 200 µM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This
unusual positive modulation is not unique to the mammalian receptor. The response of chicken hair cells exposed to
ACh likewise was enhanced in the presence of 100 µM ryanodine. This facilitatory effect on current through the AChR
also could result in greater activation of associated calcium-dependent K+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
and corresponds to an increase in the apparent affinity and efficacy for acetylcholine (ACh). Moreover, AChevoked
currents through the isolated cholinergic receptor of inner hair cells (IHCs) in excised mouse cochleas were
enhanced ~ 50% by 200 µM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This
unusual positive modulation is not unique to the mammalian receptor. The response of chicken hair cells exposed to
ACh likewise was enhanced in the presence of 100 µM ryanodine. This facilitatory effect on current through the AChR
also could result in greater activation of associated calcium-dependent K+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
and corresponds to an increase in the apparent affinity and efficacy for acetylcholine (ACh). Moreover, AChevoked
currents through the isolated cholinergic receptor of inner hair cells (IHCs) in excised mouse cochleas were
enhanced ~ 50% by 200 µM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This
unusual positive modulation is not unique to the mammalian receptor. The response of chicken hair cells exposed to
ACh likewise was enhanced in the presence of 100 µM ryanodine. This facilitatory effect on current through the AChR
also could result in greater activation of associated calcium-dependent K+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
and corresponds to an increase in the apparent affinity and efficacy for acetylcholine (ACh). Moreover, AChevoked
currents through the isolated cholinergic receptor of inner hair cells (IHCs) in excised mouse cochleas were
enhanced ~ 50% by 200 µM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This
unusual positive modulation is not unique to the mammalian receptor. The response of chicken hair cells exposed to
ACh likewise was enhanced in the presence of 100 µM ryanodine. This facilitatory effect on current through the AChR
also could result in greater activation of associated calcium-dependent K+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
and corresponds to an increase in the apparent affinity and efficacy for acetylcholine (ACh). Moreover, AChevoked
currents through the isolated cholinergic receptor of inner hair cells (IHCs) in excised mouse cochleas were
enhanced ~ 50% by 200 µM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This
unusual positive modulation is not unique to the mammalian receptor. The response of chicken hair cells exposed to
ACh likewise was enhanced in the presence of 100 µM ryanodine. This facilitatory effect on current through the AChR
also could result in greater activation of associated calcium-dependent K+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
and corresponds to an increase in the apparent affinity and efficacy for acetylcholine (ACh). Moreover, AChevoked
currents through the isolated cholinergic receptor of inner hair cells (IHCs) in excised mouse cochleas were
enhanced ~ 50% by 200 µM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This
unusual positive modulation is not unique to the mammalian receptor. The response of chicken hair cells exposed to
ACh likewise was enhanced in the presence of 100 µM ryanodine. This facilitatory effect on current through the AChR
also could result in greater activation of associated calcium-dependent K+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
and corresponds to an increase in the apparent affinity and efficacy for acetylcholine (ACh). Moreover, AChevoked
currents through the isolated cholinergic receptor of inner hair cells (IHCs) in excised mouse cochleas were
enhanced ~ 50% by 200 µM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This
unusual positive modulation is not unique to the mammalian receptor. The response of chicken hair cells exposed to
ACh likewise was enhanced in the presence of 100 µM ryanodine. This facilitatory effect on current through the AChR
also could result in greater activation of associated calcium-dependent K+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
and corresponds to an increase in the apparent affinity and efficacy for acetylcholine (ACh). Moreover, AChevoked
currents through the isolated cholinergic receptor of inner hair cells (IHCs) in excised mouse cochleas were
enhanced ~ 50% by 200 µM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This
unusual positive modulation is not unique to the mammalian receptor. The response of chicken hair cells exposed to
ACh likewise was enhanced in the presence of 100 µM ryanodine. This facilitatory effect on current through the AChR
also could result in greater activation of associated calcium-dependent K+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
and corresponds to an increase in the apparent affinity and efficacy for acetylcholine (ACh). Moreover, AChevoked
currents through the isolated cholinergic receptor of inner hair cells (IHCs) in excised mouse cochleas were
enhanced ~ 50% by 200 µM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This
unusual positive modulation is not unique to the mammalian receptor. The response of chicken hair cells exposed to
ACh likewise was enhanced in the presence of 100 µM ryanodine. This facilitatory effect on current through the AChR
also could result in greater activation of associated calcium-dependent K+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
a9a10 nAChR expressed in Xenopus oocytes, the first such compound to be found
and corresponds to an increase in the apparent affinity and efficacy for acetylcholine (ACh). Moreover, AChevoked
currents through the isolated cholinergic receptor of inner hair cells (IHCs) in excised mouse cochleas were
enhanced ~ 50% by 200 µM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This
unusual positive modulation is not unique to the mammalian receptor. The response of chicken hair cells exposed to
ACh likewise was enhanced in the presence of 100 µM ryanodine. This facilitatory effect on current through the AChR
also could result in greater activation of associated calcium-dependent K+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.
+ (SK) channels in hair cells under conditions
that permitted this activity. This novel effect of ryanodine provides new opportunities for the design of compounds
that potentiate a9a10 mediated responses and for potential inner ear therapeutics based on this interaction.