Atrial Natriuretic Factor (ANF) Effects on L-, N-, and P/Q-Type Voltage-Operated Calcium Channels

RODRIGUEZ FERMEPIN M; ALVAREZ MAUBECIN; ZARRABEITIA V; BIANCIOTTI LG; VATTA MS; FERNADEZ BE

CELLULAR AND MOLECULAR NEUROBIOLOGY.

SPRINGER/PLENUM PUBLISHERS

Lugar: New York; Año: 2002 vol. 22 p. 771 - 781

0272-4340

1. We have previously reported that atrial natriuretic factor (ANF) decreases neuronalnorepinephrine (NE) release. The mechanism that mediates NE release from presynapticmembrane to synaptic cleft is a strongly calcium-dependent process. The modulator effectof ANF may be related to modifications in calcium influx at the presynaptic nerve endingby interaction with voltage-operated calcium channels (VOCCs).2. On this basis we investigated the effects of ANF on KC-induced 45Ca2C uptake andevoked neuronalNErelease in the presence of specific L-, N-, and P/Q-type calcium channelblockers in the rat hypothalamus.3. Results showed that ANF inhibited KC-induced 45Ca2C uptake in a concentrationdependentfashion. Concentration?response curves to VOCC blockers nifedipine (NFD, Ltypechannel blocker),$-conotoxinGVIA(CTX, N-type channel blocker), and$-agatoxinIVA (AGA, P/Q-type channel blocker) showed that all the blockers decreased NE release.Incubation ofANFplusNFDshowed an additive effect as compared toNFDorANFalone.However, when the hypothalamic tissue was incubated in the presence of ANF plus CTXor AGA there were no differences in neuronal NE release as compared to calcium channelblockers or ANF alone.4. These results suggest that ANF decreases NE release by an L-type calcium channelindependent mechanism by inhibiting N- and/or P/Q-type calcium channels at the neuronalpresynaptic level. Thus,ANFmodulates neuronalNErelease through different mechanismsinvolving presynaptic calcium channel inhibition.