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)