MUSCARINIC INHIBITION OF HIGH-VOLTAGE-ACTIVATED CALCIUM CHANNELS IN EXCISED MEMBRANES OF RAT HIPPOCAMPAL-NEURONS

The effect of muscarine on voltage-gated calcium channels was investig ated in outside-out patches from rat hippocampal neurons in culture. B y cramping the excised patches at -60 mV holding potential, single and multiple Ca channel currents were recorded, and these displayed featu res similar to the high-voltage-activated Ca current, with unitary con ductance of 6.4 pS in 50 mM external Ca2+. These channels turned out t o be insensitive both to Bay K 8644 and to omega-conotoxin. In excised patches muscarine caused a marked reduction in the probability of ope ning of this class of Ca channels without significant changes in the u nitary current amplitude. Interestingly, the degree of current inhibit ion was reduced by depolarization, thus suggesting a voltage-dependent inhibitory action of the agonist. We conclude that in hippocampal neu rons one of the possible ways of HVA Ca channel modulation by muscarin e occurs through activation of a substratum localized within the plasm a membrane of the cell, independent of the involvement of diffusible i ntracellular messengers.