Vasoactive intestinal peptide (VIP) is colocalized in parasympathetic nerve terminals in the heart and coreleased from these nerve terminals with the 'classical' neurotransmitter acetylcholine (Ach). VIP also exerts a positive inotropic effect on the intact heart and enhances adenylyl cyclase activity in isolated heart membranes. Using the whole-cell patch-clamp technique, we show here that VIP enhances Ca2+ and Ba2+ currents (I(Ba)) through voltage-dependent L-type Ca2+ channels in adult rat: ventricular myocytes. Neither the kinetics nor the voltage-dependent properties of the currents are affected. The effect of VIP on I(Ba) is dose dependent with a half-maximal concentration of approximately 0.4 μM. The onset of the effect of VIP and the recovery phase are slow, suggesting the involvement of an intracellular second messenger. The effect of VIP on I(Ba) is antagonized by a peptide analog of the growth hormone releasing factor ([Ac-Tyr1, D-Phe2 ]-GRF) which belongs to the same peptide family as VIP. Although VIP and the β-adrenergic receptor agonist isoproterenol (ISO) enhance I(Ba) peak amplitudes to approximately the same extent, the effect of VIP is not seen on all cells. Only approximately 50% of the isolated myocytes respond to 5 μM VIP, whereas 95% of the cells respond to ISO. Similar results were obtained using the amphotericin B perforated-patch whole-cell-recording technique, suggesting that the variable response to VIP does not reflect the loss of a pivotal intracellular regulator. The gastrointestinal hormone secretin, a peptide structurally related to VIP, also potentiates I(Ba) in adult rat ventricular myocytes, although secretin is substantially more potent than VIP (half-maximal, concentration for secretion is about 0.7 nM). Taken together, these results suggest that the VIP- (and secretin-) induced potentiation of I(Ba) in adult rat ventricular myocytes is mediated through a non-VIP-preferring class of VIP receptors.
- Adenylyl cyclase
- Cardiac calcium current
- Parasympathetic nervous system
- Vasoactive intestinal peptide