Parathyroid hormone: an endogenous modulator of cardiac calcium channels

We have tested the effects of the active 1-34 amino acid sequence of rat parathyroid hormone (PTH) on Ca2+ channel activity in neonatal rat ventricular cells. Rat PTH (30 pM to 10 nM) increased depolarization-induced Ca2+ influx into these cells, an effect that was abolished by 1 microM nifedipine. The 1-34 amino acid sequence of bovine PTH also stimulated Ca2+ influx in control cells but not in cells pretreated with cholera toxin. Rat PTH also elevated adenosine 3',5'-cyclic monophosphate accumulation in these ventricular myocytes. Whole cell voltage-clamp recordings confirmed a stimulatory effect of rat PTH on cardiac L-type Ca2+ channels. Cell-attached single channel recordings revealed an increase in the probability of channel opening as the primary mechanism for the enhancement of Ca2+ current. Taken together these results suggest an important role for PTH as an endogenous modulator of cardiac L-type Ca2+ channels.