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(Circulation. 1997;96:3704-3709.)
© 1997 American Heart Association, Inc.

Articles

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

Motoki Hara, MD; Yuan-Mou Liu, MD; LiCi Zhen, MD; Ira S. Cohen, MD, PhD; Hangang Yu, PhD; Peter Danilo, Jr, PhD; Kazuhide Ogino, MD, PhD; John P. Bilezikian, MD; ; Michael R. Rosen, MD

From the Departments of Pharmacology, Medicine, and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, and the Departments of Physiology and Biophysics, SUNY Stony Brook, NY.

Correspondence to Michael R. Rosen, MD, Gustavus A. Pfeiffer Professor of Pharmacology, Professor of Pediatrics, College of Physicians and Surgeons of Columbia University, Department of Pharmacology, 630 W 168 St, PH 7West-321, New York, NY 10032. E-mail franeye{at}cudept.cis.columbia.edu

Background The classic calciotropic hormone parathyroid hormone (PTH) and its paracrine factor parathyroid hormone–related protein (PTHrP) both increase heart rate.

Methods and Results We used standard electrophysiological techniques to study the effects of PTH and PTHrP on isolated rabbit sinus node, isolated canine Purkinje fibers, and disaggregated 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 increased at PTH and PTHrP 10 nmol/L (P<.05). Comparable results were seen in canine Purkinje fibers. We then used the perforated-patch technique to study the I_f pacemaker current in sinus node. 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 both agents were reversible. The increase in I_f appeared to result from a change in maximal conductance and not a shift in the voltage dependence of activation.

Conclusions These observations provide, for the first time, direct electrophysiological support for the chronotropic actions of PTH and PTHrP. They suggest that classic hormones and paracrine factors can have multiple functions and that in the case of PTH and PTHrP, a newly recognized action is to alter automaticity directly.

Key Words: hormones • peptides • heart rate

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