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KMID : 0811720070110000088
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Korean Journal of Physiology & Pharmacology
2007 Volume.11 No. 0 p.88 ~ p.0
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CaMKII Inhibition Decreases Na+ Currents in Rat Ventricular Myocytes
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Yoon Jin-Young
Lee Suk-Ho
Ho Won-Kyung
Cho Ha-Na
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Abstract
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The voltage-gated Na channel (VGSC) is the major determinant underlying the upstroke phase of the action potential (AP) in most excitable cells. Nine genes encoded the α-subunit in mammals, with the proteins designated NaV1.1-1.9. The majority of these subtypes are expressed in neurons, but NaV1.4 and NaV1.5 are expressed primarily in skeletal and cardiac muscle, respectively. The gating of VGSC is modulated by various intracellular signal transduction mechanisms and by drugs. Reported effects of Ca2+, calmodulin(CaM), Ca2+/CaM-dependent kinase (CaMK) upon the cardiac NaV1.5 channel have been particularly discordant. It may be probable that the expressed CaM or ion channels in recombinant system behave differently, compared to those in native environment. In the present study, we investigated whether CaM, or CaMKII modulates cardiac Na+ channels using rat ventricular myocytes. Here, we demonstrated that Ca did not alter the function of native Na+ channel in rat ventricular myocytes. To avoid the problem of voltage escape, activation of Ina was recorded in low external [Na+]. Steady-state inactivation of Ina was not modulated by chaging intracellular EGTA (0.1 mM) with BAPTA (10 mM) or substrating extracellar Ca2+(1.8 mM) to Ba2+. Inhibition of CaMKII by KN-93 (5μM), reduced Na+ current (INA), and shifted the availability curve to more hyperpolarized potentials. In addition, protein alkaline phosphatase (10 unit/ ml) caused similar effects as induced by CaMKII inhibition. Spontaneous shift of V1/2 of vailability curve was decreased by alkaline phosphatase. These results suggest that Ca2+ does not directly act on Na+ channels. Alternatively, CaMKII regulates Na+ channel function in cardiac myocytes, most likely by phosphorylation of Na+ channels.
Source: Korean Journal of Physiology & Pharmacology.2007 Oct;11(Suppl II):S82-S82
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KEYWORD
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Na+ channel, Ca2+, CaMK, KN-93
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