Calcium channels controlling acetylcholine release from preganglionic nerve terminals in rat autonomic ganglia

Little is known about the nature of the calcium channels controlling neurot ransmitter release from preganglionic parasympathetic nerve fibres. In the present study, the effects of selective calcium channel antagonists and ami loride were investigated on ganglionic neurotransmission. Conventional intr acellular recording and focal extracellular recording techniques were used in rat submandibular and pelvic ganglia, respectively. Excitatory postsynap tic potentials and excitatory postsynaptic currents preceded by nerve termi nal impulses were recorded as a measure of acetylcholine release from paras ympathetic and sympathetic preganglionic fibres following nerve stimulation . The calcium channel antagonists omega-conotoxin GVIA (N type), nifedipine and nimodipine (L type), omega-conotoxin MVIIC and omega-agatoxin IVA (P/Q type), and Ni2+ (R type) had no functional inhibitory effects on synaptic transmission in both submandibular and pelvic ganglia. The potassium-sparin g diuretic, amiloride, and its analogue, dimethyl amiloride, produced a rev ersible and concentration-dependent inhibition of excitatory postsynaptic p otential amplitude in the rat submandibular ganglion. The amplitude and fre quency of spontaneous excitatory postsynaptic potentials and the sensitivit y of the postsynaptic membrane to acetylcholine were unaffected by amilorid e. In the rat pelvic ganglion, amiloride produced a concentration-dependent inhibition of excitatory postsynaptic currents without causing any detecta ble effects on the amplitude or configuration of the nerve terminal impulse . These results indicate that neurotransmitter release from preganglionic par asympathetic and sympathetic nerve terminals is resistant to inhibition by specific calcium channel antagonists of N-, L-, P/Q- and R-type calcium cha nnels. Amiloride acts presynaptically to inhibit evoked transmitter release , but does not prevent action potential propagation in the nerve terminals, suggesting that amiloride may block the pharmacologically distinct calcium channel type(s) on rat preganglionic nerve terminals. (C) 1999 IBRO. Publi shed by Elsevier Science Ltd.