In this study, we investigated the modulation of calcium channels by vasoactive intestinal polypeptide (VIP) in hamster submandibular ganglion (SMG) cells using the whole-cell patch clamp technique. VIP (1 microM) inhibited the high voltage-gated calcium channels in the SMG neurons via activation of VIP receptors and G-protein coupled to these receptors, but did not affect the low voltage-gated calcium channels. VIP at 1 microM reduced the peak amplitude of the maximum high voltage-gated calcium current by 26.0 +/- 6.2% (mean +/- S.E., n = 5) and slowed the rising phase of the calcium current. The time to peak of the maximum high voltage-gated calcium current was prolonged from 16.8 msec to 22.4 msec. In a representative cell, 1 microM VIP reduced the peak amplitude of maximum high voltage-gated calcium current by 50.5% and the amplitude at the end of voltage step after 300 msec by 51.9%. The VIP-induced inhibition of the calcium current was produced in a voltage-dependent manner. Inhibition was maximal (50.5%) at the level of -20 mV. Therefore, VIP inhibits both transient and sustained types of high voltage-gated calcium channels in the hamster SMG neuron.