Related Experiment Videos
Relaxin increases heart rate by modulating calcium current in cardiac pacemaker cells
1Department of Medical Physiology, University of Calgary School of Medicine, Alberta, Canada.
Circulation Research
|March 1, 1994
Summary
Relaxin (RLX) increases heart rate by enhancing L-type calcium currents in sinoatrial node cells. This effect is mediated by cyclic AMP (cAMP) and protein kinase activation, providing electrophysiological evidence for RLX
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Molecular Cardiology
Background:
- Relaxin (RLX), an insulin-family reproductive hormone, is known to increase heart rate in animal models.
- The precise cellular and ionic mechanisms underlying RLX's positive chronotropic effect are not fully understood.
Purpose of the Study:
- To investigate the electrophysiological actions of RLX on sinoatrial node cells.
- To elucidate the ionic currents and signaling pathways involved in RLX-mediated heart rate modulation.
Main Methods:
- Whole-cell voltage-clamp recordings from single rabbit sinoatrial node cells.
- Nystatin-perforated-patch and membrane-ruptured patch techniques were employed.
- Measurement of action potentials and transmembrane ionic currents, including L-type calcium current (ICa(L)).
Main Results:
- RLX (0.8-80 nmol/L) reversibly increased spontaneous action potential rate and dose-dependently augmented ICa(L).
- RLX's effects were blocked by inhibiting cAMP-dependent protein kinase (PKI) and were absent after isoprenaline or cAMP/8-Br-cAMP application.
- A Langmuir fit indicated a threshold concentration of 1 nmol/L and a KD of 14 nmol/L for ICa(L) augmentation.
Conclusions:
- RLX modulates heart rate and contractility by increasing ICa(L) in sinoatrial node cells.
- The mechanism involves increased intracellular cyclic AMP (cAMP) and activation of cAMP-dependent protein kinase.
- This study provides the first electrophysiological evidence for RLX's chronotropic effects via the cAMP/PKA pathway.