Agatoxin-IVA-sensitive calcium channels mediate the presynaptic and postsynaptic nicotinic activation of cardiac vagal neurons

Whole cell currents and miniature glutamatergic synaptic events (minis) wer e recorded in vitro from cardiac vagal neurons in the nucleus ambiguus usin g the patch-clamp technique. We examined whether voltage-dependent calcium channels were involved in the nicotinic excitation of cardiac vagal neurons . Nicotine evoked an inward current, increase in mini amplitude, and increa se in mini frequency in cardiac vagal neurons. These responses were inhibit ed by the nonselective voltage-dependent calcium channel blocker Cd (100 mu M). The P-type voltage-dependent calcium channel blocker agatoxin IVA (100 nM) abolished the nicotine-evoked responses. Nimodipine (2 muM), an antagon ist of L-type calcium channels, inhibited the increase in mini amplitude an d frequency but did not block the ligand gated inward current. The N- and Q -type voltage-dependent calcium channel antagonists conotoxin GVIA (1 muM) and conotoxin MVIIC (5 muM) had no effect. We conclude that the presynaptic and postsynaptic facilitation of glutamatergic neurotransmission to cardia c vagal neurons by nicotine involves activation of agatoxin-IVA-sensitive a nd possibly L-type voltage-dependent calcium channels. The postsynaptic inw ard current elicited by nicotine is dependent on activation of agatoxin-IVA -sensitive voltage-dependent calcium channels.