Presynaptic calcium channels mediating synaptic transmission in submucosal neurones of the guinea‐pig caecum

1 Intracellular recording techniques were used to examine the voltage‐activated calcium channels mediating neurotransmitter release from nerve terminals of extrinsic, sympathetic origin and intrinsic (enteric) origin innervating submucosal neurones of the guinea‐pig caecum. 2 The noradrenergic slow inhibitory postsynaptic potential (IPSP) was abolished by superfusion of ω‐conotoxin (ω‐CTX) GVIA (3‐300 nM), with an apparent IC 5 0 of 8.6 nM. Superfusion of ω‐CTX MVIIC (500 nM) also suppressed the amplitude of slow IPSPs, but both ω‐agatoxin IVA (100 nM) and nicardipine (1‐10 μM) were ineffective. The hyperpolarization induced by exogenous noradrenaline was not affected by ω‐CTX GVIA (100 nM). 3 In contrast to the slow IPSP, the amplitude of the cholinergic fast excitatory postsynaptic potential (EPSP) was partially inhibited, but not abolished, by ω‐CTX GVIA (0.1‐1 μM). Furthermore, ω‐agatoxin IVA (0.1‐1 μM) or ω‐CTX MVIIC (0.1‐1 μM) also affected the fast EPSP, but nicardipine (1–10 μM) was ineffective. In combination, ω‐CTX GVIA (100 nM) and ω‐agatoxin IVA (100 nM) inhibited the fast EPSP by 74 ± 6 %; the residual fast EPSP was not affected by ω‐CTX MVIIC (100 nM). The fast EPSP was completely abolished by low Ca 2+ , high Mg 2+ Krebs solution or Krebs solution containing Co 2+ (2 mM) and Cd 2+ (400 μM). The depolarization induced by exogenous acetylcholine was not affected by either ω‐CTX GVIA (100 nM), ω‐agatoxin IVA (100 nM) or ω‐CTX MVIIC (100 nM). 4 Taken together, these results suggest that, in the submucosal plexus of the guinea‐pig caecum, release of noradrenaline from extrinsic nerve terminals is regulated by N‐type calcium channels, whereas release of acetylcholine from intrinsic nerve terminals involves several types of calcium channel.