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RISS 인기검색어
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- 저자 : Hankyoun Kim (검색결과 1 건)
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Jin Han,Nari Kim,Euiyong Kim,Wonkyung Ho,Yung E Earm,Hankyoun Kim 대한생리학회-대한약리학회 1998 The Korean Journal of Physiology & Pharmacology Vol.2 No.6
<P> <I> </I>Background: We have previously reported that not only cGMP but also 8-Br-cGMP or 8-pCPT-cGMP, specific and potent stimulators of cGMP-dependent protein kinase (cGMP-PK), increased basal L-type calcium current (I<SUB>Ca</SUB>) in rabbit ventricular myocytes. Our findings in rabbit ventricular myocytes were entirely different from the earlier findings in different species, suggesting that the activation of cGMP-PK is involved in the facilitation of I<SUB>Ca</SUB> by cGMP. However, there is no direct evidence that cGMP-PK can stimulate I<SUB>Ca</SUB> in rabbit ventricular myocytes. In this report, we focused on the direct effect of cGMP-PK on I<SUB>Ca</SUB> in rabbit ventricular myocytes. Methods and Results: We isolated single ventricular myocytes of rabbit hearts by using enzymatic dissociation. Regulation of I<SUB>Ca</SUB> by cGMP-PK was investigated in rabbit ventricular myocytes using whole-cell voltage clamp method. I<SUB>Ca</SUB> was elicited by a depolarizing pulse to 10 mV from a holding potential of 40 mV. Extracellular 8-(4-Chlorophenylthio)-guanosine-3 ,5 -cyclic monophosphate (8-pCPT-cGMP), potent stimulator of cGMP-dependent protein kinase (cGMP-PK), increased basal I<SUB>Ca</SUB>. cGMP-PK also increased basal I<SUB>Ca</SUB>. The stimulation of basal I<SUB>Ca</SUB> by cGMP-PK required both 8-Br-cGMP in low concentration and intracellular ATP to be present. The stimulation of basal I<SUB>Ca</SUB> by cGMP-PK was blocked by heat inactivation of the cGMP-PK and by bath application of 8- (4-chlorophenylthio)-guanosine-3 ,5 -cyclic monophosphate, Rp-isomer (Rp-pCPT-cGMP), a phosphodiesterase-resistant cGMP-PK inhibitor. When I<SUB>Ca</SUB> was increased by internal application of cGMP-PK, IBMX resulted in an additional stimulation of I<SUB>Ca</SUB>. In the presence of cGMP-PK, already increased I<SUB>Ca</SUB> was potentiated by bath application of isoprenaline or forskolin or intracellular application of cAMP. Conclusions: We present evidence that cGMP-PK stimulated basal I<SUB>Ca</SUB> by a direct phosphorylation of L-type calcium channel or associated regulatory protein in rabbit ventricular myocytes.
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