Effects of neuropeptide Y on L-type calcium current in guinea-pig ventricular myocytes.
1. Neuropeptide Y (NPY) reduces cell shortening at high concentrations in guinea-pig ventricular myocytes. We have studied the effects of the peptide on calcium current in cardiac myocytes. 2. We have recorded L-type calcium current in guinea-pig ventricular myocytes under conditions in which the effects of other overlapping currents have been minimised by using Na(+)-free, K(+)-free external solution and patch-clamp electrodes containing Cs+. 3. Peak inward calcium current is reduced by NPY at concentrations in excess of 1 nM, and maximal inhibition (31%) was found at and above concentrations of 100 nM. The IC50 value for NPY inhibition of peak calcium current was 1.72 nM. 4. NPY had no effect on the voltage-dependence of calcium current amplitude, on the time course of current inactivation, or on the voltage-dependence of the steady-state gating variables. 5. NPY did not reduce the calcium current in the presence of 8-Br-cyclic AMP, and it was also without effect when GTP-gamma-S or GDP-beta-S were included in the patch pipette. 6. We conclude that in guinea-pig ventricular myocytes NPY acts at low concentration to reduce L-type calcium current, via a G-protein-mediated pathway and reduction in intracellular cyclic AMP.
Bryant
S M
SM
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital.
Hart
G
G
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D013268:Stimulation, Chemical
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009478:Neuropeptide Y; D006160:Guanosine Triphosphate; D000242:Cyclic AMP