PRESYNAPTIC CALCIUM CHANNELS AND TEMPORAL PRECISION OF NEUROTRANSMITTER RELEASE AT NORMAL AND P/Q-TYPE DEFICIENT MOUSE NEUROMUSCULAR JUNCTION

RAFAEL S DEPETRIS, SILVANA I NUDLER, FRANCISCO J URBANO, ERIKA S PIEDRAS-RENTERIA, RICHARD W TSIEN, OSVALDO D UCHITEL

Buenos Aires, Argentina

Congreso; XIV International Biophysics Congress; 2002

International Union for Pure and Applied Biophysics

Abstract Neuromuscular (NM) transmission in P/Q  deficient mice has a low quantal content and is mediated b y N- and R-type channels. Here we studied the timing of transmitter release, using extracellular recordings obtained with low resistant microelectrodes positioned onto fluorescently labeled NM junctions. Measurements of “jitter”—the variation in the time interval between the presynaptic action potential and the evoked end plate potential—were expressed as SD of the mean. The jitter was (µsec) 23 ± 1 in WT and 78.0 ± 1.7 in KO mice, respectively (mean ± S.E.M., n:11; 12, P<0.05), indicating less precisely timed neurotransmitter release in the KO mice. Synchrony was achieved by increasing extracellular calcium to 4  mM (30.00 ± 7.00, P<0.05, n>100) and reduced by blocking calcium influx with ω-conotoxin (270.00 ± 7.00, n>100, P<0.001). Jitter was also induced in WT mice by changing [Ca2+/Mg2+]o to 0.5 / 2 mM (110 ± 20 n:10, P<0.05), and by reducing the number of functional P/Q type channels with 30 nM ω-Aga IVA (60 ± 7, n:19, P<0.05). Thus, jitter of transmitter release arises from reduced peak calcium concentration at the release site, possibly due to a change in the spatial distribution of available Ca2+ channels.