| Popis: |
Voltage-gated sodium channels are crucial to action potential propagation in excitable tissues. Because of the high amplitude and rapid activation of the sodium current, voltage-clamp measurements are very challenging and are usually performed at room temperature. In this study, we measured sodium current voltage dependence in stem cell-derived cardiomyocytes at physiological temperature. While the apparent activation and inactivation curves, measured as the dependence of current amplitude on voltage step, fall within the range reported in previous studies, we identified a systematic error in our measurements. This error is caused by the deviation of the membrane potential from the command potential of the amplifier. We demonstrate that it is possible to account for this artifact using computer simulation of the patch-clamp experiment. We obtained surprising results through patch-clamp model optimization: the half-activation of -11.5 mV and the half-inactivation of -87 mV. Although the half-activation deviates from the previous research, we demonstrate that this estimate explains the conduction velocity dependence on extracellular potassium concentration. |
