constantly hyperpolarized. The bradyeardia was caused mainly by a reduction in the rate of depolarization in the later phase of the pacemaker depolarization. The bradyeardia elicited by nickel was due neither to blockade of the hyperpolarizationactivated inward current nor to inhibition of the delayed rectifier potassium current.9. It was concluded that the transient type calcium channel exists in the cardiac nodal cell and that the current participates in the later half of the slow diastolic depolarization.

In a wide variety of cells, various intracellular agents, such as Ca2+, ATP and cyclic nucleotides, regulate ionic conductances of the membrane. In cardiac cells, the intracellular Na+ concentration [( Na+]i) frequently increases when a disturbance occurs in the electrogenic Na-K pump activity or the Na-Ca exchange mechanism. We have investigated a possible role of [Na+]i in controlling ion channels by using a patch-clamp method, and have found a K+ channel that is gated by [Na+]i greater than 20 mM, but not by the intracellular Ca2+ concentration (approximately 10(-4) M). We report here that the channel has a unitary conductance of 207 +/- 19 pS (n = 16) with K+ concentrations of 150 mM outside and 49 mM inside, and shows no detectable voltage-dependent kinetics. The Na+-activated K+ channel represents a novel class of ionic channel.

No abstract

Dose-response relations for the increase in the amplitude of Ca current (ICa) on external application of isoprenaline (ISP) and internally applied cyclic AMP (cAMP) or catalytic subunit of cAMP-dependent protein kinase (C subunit) were established in single ventricular cells of the guinea pig. An intracellular dialysis technique was used. The threshold concentration was for ISP 10(-9) M, for cAMP 3 microM (pipette concentration to which 10(-5) M 3-isobutyl-1-methylxanthine was added) and for C subunit around 0.4 microM (pipette concentration). The concentrations for the half-maximal effect were 3.7 X 10(-8) M (ISP), 5.0 microM (cAMP) and 0.95 microM (C subunit) and for the maximum effect 10(-6) M (ISP), 15-20 microM (cAMP) and 3-4 microM (C subunit). For all three agents the maximum increase in the Ca current density was similar (a factor of 3-4), suggesting that they converge on the same site of the Ca channel. Accordingly, the effects of cAMP and C subunit on ICa were non-additive to those of ISP. From these data the relationship both between concentrations of ISP and cAMP and between those of cAMP and active C subunit in terms of their effects on ICa could be estimated and were compared with those obtained in broken cell preparations. A competitive inhibitor of phosphorylation, 5'-adenylyl-imidodiphosphate (5 mM), greatly reduced the effects of ISP and C subunit on ICa. Cell dialysis with 3 mM adenosine-5'-(gamma-thio)-triphosphate, which produces a dephosphorylation-resistant phosphorylation, markedly potentiated the effects of ISP and cAMP on ICa.(ABSTRACT TRUNCATED AT 250 WORDS)