VIP and secretin augment cardiac L-type calcium channel currents in isolated adult rat ventricular myocytes.
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 (IBa) 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 IBa is dose dependent with a half-maximal concentration of approximately 0.4 microM. 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 IBa 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 beta-adrenergic receptor agonist isoproterenol (ISO) enhance IBa 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 microM 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 IBa in adult rat ventricular myocytes, although secretin is substantially more potent than VIP (half-maximal concentration for secretin is about 0.7 nM). Taken together, these results suggest that the VIP- (and secretin-) induced potentiation of IBa in adult rat ventricular myocytes is mediated through a non-VIP-preferring class of VIP receptors.
Tiaho
F
F
Department of Molecular Biology and Pharmacology, Box 8103, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, MO 63110, USA.
Nerbonne
J M
JM
D000818:Animals; D001464:Barium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012633:Secretin / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; D012633:Secretin; D001464:Barium; D014660:Vasoactive Intestinal Peptide; D007545:Isoproterenol