Two types of voltage-dependent calcium channel currents and their modulation by parathyroid hormone in neonatal rat ventricular cells.
The positive inotropic and chronotropic actions of parathyroid hormone (PTH) in cardiac cells are considered to be related to the modulation of calcium influx. The underlying mechanisms, however, are unknown, and direct electrophysiological evidence at the single-cell level is required. In the present study, the whole-cell configuration of the patch-clamp technique was used in neonatal rat ventricular cells to identify both transient (T) and long-lasting (L) voltage-dependent calcium channels according to their electrophysiological and pharmacological characteristics. The active synthetic fragment of bovine PTH, bPTH-(1-34), at a concentration of 1 microM, significantly enhanced the magnitude of L-channel currents by 67.8% (n = 13, p less than 0.01). The steady-state activation curve of L-channel currents was shifted along the voltage axis toward more negative potentials by either bPTH-(1-34) or Bay K-8644. The suppression or amplification of PTH-induced enhancement of inward currents by nifedipine, 1 microM, or Bay K-8644, 5 microM, respectively, further indicated that the effect of PTH was specific for L-type calcium channels. However, bPTH-(1-34) failed to modulate the magnitude or kinetics of T-channel currents. This study directly demonstrates that PTH is a specific endogenous calcium-channel activator in neonatal rat ventricular cells.
Wang
R
R
Department of Physiology, University of Alberta, Edmonton, Canada.
Karpinski
E
E
Pang
P K
PK
D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats
D015220:Calcium Channels; D004095:Dihydropyridines; D010281:Parathyroid Hormone; D010446:Peptide Fragments; C025076:parathyroid hormone (1-34), bovine