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KMID : 0811720070110000079
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Korean Journal of Physiology & Pharmacology
2007 Volume.11 No. 0 p.79 ~ p.0
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The Mitochondrial Ca2+-activated K+ Channel Activator, NS 1619 Inhibits L-type Ca2+ Channels in Rat Ventricular Myocytes
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Kang Sung-hyun
Park Won-Sun
Kim Hyoung-Kyu
Han Jin
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Abstract
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We examined the effects of the mitochondrial Ca2+-activated K+ (mitoBKCa) channel activator NS 1619 on L-type Ca2+ channels in rat ventricular myocytes using the whole-cell patch clamp technique. NS 1619 inhibited the Ca2+ current in a dose-dependent manner with a Kd value of 6.52μM. NS 1619 shifted the activation curve to more positive potentials, but did not have a significant effect on the voltage dependence of the inactivation curve. Pretreatment with a membrane BKCa (membBKCa) channel inhibitor (iberiotoxin), mitoBKCa channel inhibitor (paxilline), protein kinase C inhibitor (GF 109203X), protein kinase A inhibitor (RP-8-CPT-cAMPs), and protein kinase G inhibitor (RP-8-Br-PET-cGMPs) had little effect on the Ca2+ current and did not alter the inhibitory effect of NS 1619 significantly. Furthermore, the application of intracellular ATP-free solution did not alter the effect of NS 1619. The application of additional NS 1619 in the presence of isoproterenol (1μM), a selective β-adrenoreceptor agonist, reduced the Ca2+ current to approximately the same level as a single application of NS 1619. In conclusion, our results suggest that NS 1619 inhibits the Ca2+ current independent of the mitoBKCa channel and protein kinases. Since NS 1619 is widely used to study mitoBKCa channel function, it is essential to verify these unexpected effects of NS 1619 before experimental data can be interpreted accurately.
Source: Korean Journal of Physiology & Pharmacology.2007 Oct;11(Suppl II):S78-S78
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KEYWORD
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Mitochondrial Ca2+-activated K+ channel, NS 1619, L-type Ca2+ channel, Ventricular myocytes
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