LOSS OF TEMPORAL PRECISION OF NEUROTRANSMITTER RELEASE AT NEUROMUSCULAR JUNCTIONS OF MICE LACKING P/Q-TYPE CALCIUM CHANNELS

RS DEPETRIS, SI NUDLER, FJ URBANO, ES PIEDRAS RENTERIA, RW TSIEN, OD UCHITEL

San Diego, CA, USA

Congreso; Society for Neuroscience's 31st Annual Meeting; 2001

Society for Neuroscience

Abstract. The absence of P/Q Ca2+ channels in the α1A (Cav2.1) null mutant mice induces dystonia, ataxia and death (~P21). Neuromuscular (NM) transmission in mutant mice has a low quantal content and is mediated by N- and R-type rather than P/Q-type channels (Urbano et al., Biophysical Society 2001 Abstract). Here we focused on timing of transmitter release, using extracellular recordings obtained with low resistance microelectrodes positioned at fluorescently labeled NM junctions. Measurements of the variation in the time interval between the presynaptic action potential and the evoked end plate potential (jitter) were expressed as SD. The jitter (µs) was 23±1 in WT and 78.0±1.7 in α1A-/- mice (mean+S.E.M., n:11,12, P<0.05), indicating a loss of temporal presicion in the KO. Qualitatively similar effects were produced in at WT NMJ by      lowering [Ca2+/Mg2+]o to 0.5/2 mM (110±20 µs, n:10, P<0.05), or by reducing the number of functional P/Q type channels with 30 nM ω-Aga IVA (60±7 µs, n:19, P<0.05). Thus, in mice lacking a1A subunits, variable timing of transmitter release indicates a reduction in the average peak Ca2+ concentration at the release site. Our earlier experiments with BAPTA and EGTA suggest that this may arise from an altered spatial distribution of available Ca2+ channels in the absence of α1A.