The effects of an adenylate cyclase inhibitor on the electrophysiological correlates of neuromuscular transmission in the frog.
The presynaptic and postsynaptic effects of MDL 12,330A, an adenylate cyclase inhibitor in several biological tissues, were studied at motor endplates in frog cutaneous pectoris nerve-muscle preparations. This agent increased both spontaneous quantal acetylcholine (ACh) release and neurally-evoked ACh release approximately twofold during the first 20-40 min of application. The increased ACh release was accompanied by a profound irreversible depression in the amplitudes of the miniature endplate potentials (m.e.p.ps) and endplate potentials (e.p.ps). The response to iontophoretically-applied ACh was reduced in parallel with the amplitude of the spontaneous m.e.p.ps, indicating that the depression of synaptic transmission was postsynaptic in origin. Endplates were voltage-clamped to study the postsynaptic depression in more detail. It was observed that the peak endplate current (e.p.c.) was depressed without concomitant changes in: the kinetics of e.p.c. decay, the relationship between peak e.p.c. and membrane potential, the ACh equilibrium potential or the voltage sensitivity of the e.p.c. decay. This suggests that MDL 12,330A reduces the postsynaptic sensitivity to ACh by a voltage-dependent block of the cholinoceptor. The presynaptic enhancement and the postsynaptic depression of junctional transmission produced by MDL 12,330A are discussed in conjunction with current theories of the role of adenylate cyclase and cyclic nucleotides at nicotinic cholinergic synapses.
D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D004594:Electrophysiology; D007097:Imines / Q000494:pharmacology*; D007478:Iontophoresis; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D011894:Rana pipiens; D011896:Rana temporaria; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D000067956:Adenylyl Cyclase Inhibitors; D007097:Imines; C014925:RMI 12330A; D000109:Acetylcholine