首页|H-89 inhibits transient outward and inward rectifier potassium currents in isolated rat ventricular myocytes
H-89 inhibits transient outward and inward rectifier potassium currents in isolated rat ventricular myocytes
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
NETL
NSTL
1 Voltage clamp was used to investigate the effects of N-[2-p-bromo-cinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), a potent inhibitor of PKA, on transient outward K~+ current (I_(to)) and inward rectifying K~+ current (I_(K1)) in rat cardiac muscle. 2 Initial experiments, performed using descending voltage ramps, showed that H-89 inhibited both the outward and inward ramp currents in a concentration-dependent manner at concentrations between 5 and 60 μmol 1~(-1). A similar degree of inhibition was observed when I_(to) and I_(K1) were recorded using square wave depolarising and hyperpolarising voltage steps, respectively. 3 The IC_(50) was 35.8 μmol 1~(-1) for I_(to) and 27.8 μmol 1~(-1) for I_(K1) compared to 5.4 μmol 1~(-1) for L-type Ca~(2+) current (I_(Ca)). The Hill coefficients for I_(to), I_(K1) and I_(Ca) were -1.97, -1.60 and -1.21, respectively. In addition to inhibiting I_(to) amplitude, H-89 also accelerated the time to peak and the rate of voltage-dependent inactivation so that the time course of I_(to) was abbreviated. 4 Paired-pulse protocols were performed to study the effects of H-89 on steady-state activation and inactivation as well as recovery from voltage-dependent inactivation. H-89 produced a concentration-dependent rightward shift in voltage-dependent activation but had no significant effect on steady-state inactivation. Recovery from voltage-dependent inactivation was delayed, although this was only visible at the highest concentration (60 μmol 1~(-1)) used. 5 In experiments investigating the effects of elevated cyclic AMP, the β-adrenergic agonist isoprenaline and the phosphatase inhibitor calyculin A had no major effects on I_(to) or I_(K1). 6 Data suggest that the effects of H-89 on K~+ currents are more complex than simple inhibition of PKA-mediated phosphorylation.
K~+ currentsH-89myocytesPKAphosphorylation
Charles Pearman、William Kent、Nicolas Bracken、Munir Hussain
展开 >
School of Clinical Sciences, University of Liverpool, Daulby Street, Liverpool L69 3GA
NETL
NSTL
