VIP and PACAP Inhibit L-, N- and P/Q-Type Ca2+ Channels of Parasympathetic Neurons in a Voltage Independent Manner.

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In this study, we investigated the effects of vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide 1-38 (PACAP) on the voltagegated calcium currents in hamster submandibular ganglion neurons. VIP and PACAP inhibited the high threshold voltage-gated calcium current in a voltage-independent and a concentration-dependent manner via the G protein-mediated pathway. L-, N- and P/Q-type components of the total maximum voltage-gated calcium current accounted for 48.0±3.1% (n=4), 35.1±4.7% (n=4), and 13.5±2.3% (n=3) of the total peak amplitude, respectively. VIP at a concentration of 1μM inhibited the L-type calcium current by 33.2%±1.4% (n=4), the N-type current by 31.0±3.6%, and the P/Q-type current by 3.2±1.1% (n=3). PACAP at a concentration of 1μM inhibited the L-type current by 35.6±5.7%, the N-type current by 34.4±3.1% (n=4), and the P/Q-type current by 6.4±2.1% (n=2). However, VIP and PACAP did not inhibit the low threshold voltagegated (T-type) calcium current. The rank order of potency was PACAP>VIP. In experiments replacing GTP with GDP-β-S, the inhibitory effects of VIP and PACAP were prevented. In experiments of double-pulse protocol, depolarizing conditioning pulses could not relieve the inhibition of total high threshold voltage-gated calcium currents produced by VIP and PACAP. Therefore, the inhibition of the high threshold voltage-gated calcium channels produced by VIP and PACAP in hamster parasympathetic neurons differed in its mechanisms from that of N-type calcium channels in rat sympathetic neurons.

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