Hyperpolarization-activated inward current in embryonic chick cardiac myocytes: developmental changes and modulation by isoproterenol and carbachol.
Modulation of the hyperpolarization-activated inward current (If) in embryonic chick ventricular myocytes was examined using whole-cell voltage-clamp. Long (3 s) hyperpolarizing pulses were applied from a holding potential of -30 mV to steps of -40 to -120 mV. If was marked in 3-day-old cells, diminished at 10 days, and was almost completely gone at 17 days. If current density (at -120 mV) was -6.7 +/- 1.3 (3 days), -3.3 +/- 1.0 (10 days), and -2.0 +/- 0.5 pA/pF (17 days). If reduction paralleled the decrease in spontaneous activity. In 3-day cells, the threshold potential was -50 to -60 mV, and the reversal potential was -13.4 +/- 1.3 mV. The time course of activation was fitted by a single exponential and was temperature dependent: tau was 1.3 +/- 0.4 s at 20 degrees C and 0.7 +/- 0.4 s at 30 degrees C (at -120 mV). If amplitude was enhanced by 12.1 +/- 1.8% at 30 degrees C compared with 20 degrees C. Cs+ (3 mM) blocked If and had a negative chronotropic effect (rate decreased by 61%). Isoproterenol (1 microM) caused a positive chronotropic effect (17.1 +/- 2.9%) and increased If by 65.2 +/- 5.6%. Carbachol (0.1 microM) had a negative chronotropic effect (26.3 +/- 3.4%), and decreased If by 41.2 +/- 1.3%; it also reversed the enhancement produced by isoproterenol. Intracellular application of 100 microM GTP-gamma S decreased basal If by 35.2 +/- 5.0%, but potentiated the stimulant effect of isoproterenol (by 37.8 +/- 4.7%) and the inhibitory effect of carbachol (21.2 +/- 4.3%).(ABSTRACT TRUNCATED AT 250 WORDS)
Satoh
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Department of Physiology and Biophysics, University of Cincinnati College of Medicine, OH 45267.
Sperelakis
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D002642:Chick Embryo; D004594:Electrophysiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D007545:Isoproterenol / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013696:Temperature
D011943:Receptors, Adrenergic, beta; D002586:Cesium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002217:Carbachol; D007545:Isoproterenol