| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
We have demonstrated that the conductance and kinetics of I_K in SA node cells closely resembled those of the rapidly activating component of I_K (I_<Kr>) which is coded by human eag-related gene (HERG), in terms of ion selectivity, gating parameters of activation, inward rectification of the steady-state IV relation, the single channel conductance, and selective blockage by class III antiarrythmic agents. The inward rectifying property was characterized by decrease of open probablity at positive potentials. Under the inside-out mode, the open probabilty did not increase even if the patch membrane was exposed to the solution containing on Mg^<2+> or Ca^<2+>, indicating that the inward rectification is not due to block by these cations but derived from the intirinsic gating of the I_<Kr> channels.
When the external Ca^<2+> was removed, the decay of the tail current was markedly prolonged. The effect of external Ca^<2+> was voltage-and concentration-dependent. The results indicate that the gating of I_<Kr>, which has been believed to be an intrinsic voltage-dependent mechanism, might be caused by a time-and voltage-dependent block and unblock of the I_<Kr> channels by external Ca^<2+>.
I_<Kr> is essential in maintaining the automaticity of rabbit SAN cells. To extend this hypothesis to other species, we made an attempt to isolate pacemaker cells from porcine hearts. The isolated cells exhibited spontaneous activity with beating rate of approximately 80 min-1 in normal Tyrode solution. It was found that the delayd rectifier K^+ current of porcine SAN cells consisted of the slowly activating delayd rectifier K + current, in contrast to I_<Kr> of rabbit. The different I_K might contribute to different heart rate among various species.
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