[Low extracellular pH increases the persistent sodium current in guinea pig ventricular myocytes].
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 on I(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-cell I(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) reversed the increased IN(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). Decreasing 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 of 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 was reversed by application of 1 mmol/L DTT [to 0.019+/-0.005 and (0.868+/-0.190) ms, both P<0.01 vs pH 6.5, n=6]. Furthermore, protein kinase C (PKC) inhibitor bisindolylmaleimide (BIM, 5 micromol/L) reduced the enhanced mean open probability and mean open time at pH 6.5 from 0.214+/-0.024 and (1.634+/-0.137) ms to 0.025+/-0.006 and (0.914+/-0.070) ms, respectively (both P<0.01 vs pH 6.5, n=6). The results demonstrate that low extracellular pH markedly increases I(Na.P) in guinea pig ventricular myocytes, in which activation of PKC may be involved.
Ma
Ji-Hua
JH
Cardio-Electrophysiological Research Laboratory, Medical College, Wuhan University of Science and Technology, Wuhan, China. mjhua@wust.edu.cn
Luo
An-Tao
AT
Wang
Wei-Ping
WP
Zhang
Pei-Hua
PH
D000818:Animals; D003470:Culture Media / Q000737:chemistry; D005110:Extracellular Space / Q000737:chemistry*; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology*
D003470:Culture Media; D015222:Sodium Channels; D012964:Sodium