VIP AND PACAP INHIBIT L-, N- AND P/Q-TYPE Ca CHANNELS OF PARASYMPATHETIC NEURONS IN A VOLTAGE INDEPENDENT MANNER

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-, Nand 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 1 M 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 1 M 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-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.