POSITIVE CHRONOTROPIC ACTIONS OF PARATHYROID-HORMONE AND PARATHYROID HORMONE-RELATED PEPTIDE ARE ASSOCIATED WITH INCREASES IN THE CURRENT, I-F, AND THE SLOPE OF THE PACEMAKER POTENTIAL

Background The classic calciotropic hormone parathyroid hormone (PTH) and its paracrine factor parathyroid hormone-related protein (PTHrP) b oth increase heart rate. Methods and Results We used standard electrop hysiological techniques to study the effects of PTH and PTHrP on isola ted rabbit sinus node, isolated canine Purkinje fibers, and disaggrega ted rabbit sinus node myocytes. Sinus node maximum diastolic potential , activation voltage, and amplitude were unchanged by PTH or PTHrP (P> .05). However, the slope of phase 4 and the automatic rate were increa sed at PTH and PTHrP greater than or equal to 10 nmol/L (P<.05). Compa rable results were seen in canine Purkinje fibers. We then used the pe rforated-patch technique to study the I,pacemaker current in sinus nod e. PTH 12.5 nmol/L and PTHrP 12.5 to 18 nmol/L increased I-f at -65 mV by 68 +/- 41% (n=5) and 69 +/- 50% (n 5), respectively. Actions of bo th agents were reversible. The increase in I-f appeared to result from a change in maximal conductance and not a shift in the voltage depend ence of activation. Conclusions These observations provide, for the fi rst time, direct electrophysiological support for the chronotropic act ions of PTH and PTHrP. They suggest that classic hormones and paracrin e factors can have multiple functions and that in the case of PTH and PTHrP, it newly recognized action is to alter automaticity-directly.