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Low extracellular pH increases the persistent sodium current in guinea pig ventricular myocytes

Ma Jihua, Luo Antao, Wang Weiping, Zhang Peihua

Cardio-Electrophysiological Research Laboratory,Medical College,Wuhan University of Science and Technology.Wuhan 430081,Hubei

Abstract

Whole-cell and cell-attached patch-clamp techniques were used to record the changes of persistent sodium current (Ⅰ_(Na.P)) in ventricular myocytes of guinea pig to investigate the effect of low extracellular pH onⅠ_(Na.P) and its mechanism. The results showed that low extracellular pH (7.0, 6.8 and 6.5) obviously increased the amplitude of whole-cellⅠ_(Na.P) in a [H~(+)] concentration-dependent manner. Under the condition of extracellular pH 6.5,Ⅰ_(Na.P) was markedly augmented from control (pH 7.4) value of (0.347±0.067)pA/pF to (0.817±0.137) pA/pF (P<0.01, n=6), whereas the reducing agent dithiothreitiol (DTT, 1 mmol/L) could reverse the increased I_(Na.P) from (0.817±0.137) pA/pF to (0.233±0.078) pA/pF (P<0.01 vs pH 6.5, n=6). Reducing extracellular pH to 6.5 also increased the persistent sodium channel activity in cell-attached patches. The mean open probability and mean open time were increased from control value 0.021±0.007 and (0.899±0.074) ms to 0.205±0.023 and (1.593±0.158) ms, respectively (both P<0.01, n=6), and such enhancement could be reversed by application of 1 mmol/L DTT [to 0.019±0.005 and (0.868±0.190) ms, both P<0.01, n=6]. Furthermore, protein kinase C (PKC) inhibitor bisindolylmaleimide (BIM) 5 #mu#mol/L reduced the enhanced mean open probability and mean open time in pH 6.5 from 0.214±0.024 and (1.634±0.137) ms to 0.025±0.006 and (0.914±0.07) ms, respectively (both P<0.01, n=6). The results demonstrate that low extracellular pH can markedly increase the I_(Na.P) in guinea pig ventricular myocytes, in which activation of PKC may be invoveled.

Key words: persistent sodium current;pH;Protein kinase C;ventricular myocytes

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Citing This Article：

Ma Jihua, Luo Antao, Wang Weiping, Zhang Peihua. Low extracellular pH increases the persistent sodium current in guinea pig ventricular myocytes. Acta Physiol Sin 2007; 59 (2): 233-239 (in Chinese with English abstract).