Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Jul 1995
Electrophysiological demonstration and activation of mu-opioid receptors in the rabbit sinoatrial node.
To investigate the presence of opioid receptors and their physiological role in cardiac pacemaker cells, we studied electrophysiological effects of fentanyl citrate, an activator of the mu-opioid receptors, on the spontaneous action potential (AP) and membrane currents, using small preparations (0.2 x 0.2 x 0.1 mm) of rabbit sinoatrial (SA) node (SAN). Fentanyl (0.1-3 microM) progressively decreased the AP amplitude (APA), maximal rate of depolarization (MRD), and spontaneous firing frequency (SFF) and prolonged the AP duration (APD) and diastolic interval in a concentration-dependent manner. ⋯ In voltage-clamp experiments using double microelectrode techniques, 1 microM fentanyl reduced the Ca2+ current (ICa) obtained on step depolarization from -40 to 0 mV by 19.9 +/- 9.3% (p < 0.05, n = 5), the fast and slow components of the delayed rectifying K+ current (IKfast, IKslow) tail obtained on repolarization from 10 to -60 mV by 54.7 +/- 4.7 and 41.4 +/- 2.4% (p < 0.05, n = 4), and the hyperpolarization-activated inward current at -90 mV by 12.6 +/- 0.5% (p < 0.05, n = 7), respectively. The gating kinetics of ICa and IKslow were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)