Voltage clamp of the cardiac sodium current at 37 degrees C in physiologic solutions

Abstract

The cardiac sodium current was studied in guinea pig ventricular myocytes using the cell-attached patch voltage clamp at 37 degrees C in the presence of 145 mM external sodium concentration. When using large patch pipettes (access resistance, 1-2 M omega), the capacity current transient duration was typically 70 microseconds for voltage clamp steps up to 150 mV. At 37 degrees C the maximum inward sodium current peaked in approximately 200 microseconds after the onset of a clamp step and at this strong depolarization, less than 10% of the sodium current developed during the capacity transient. The sodium current developed smoothly and the descending limb of the current-voltage relationship usually spanned a range of 40 mV. Moreover, currents reduced by inactivation of sodium channels could be scaled to superimpose on the maximum current. Current tails elicited by deactivation followed a monoexponential time course that was very similar for currents of different sizes. Data obtained over a range of temperatures (15 degrees-35 degrees C) showed that the steady-state inactivation and conductance-voltage curves were shifted to more negative voltages at lower temperatures. These results demonstrate the feasibility of investigating the sodium current of mammalian cardiac cells at 37 degrees C in normal physiological solutions.

Brugada syndrome and fever: Genetic and molecular characterization of patients carrying mutations

“…Increasing the temperature significantly accelerated both the activation and inactivation kinetics of WT and L325R I Na (Fig. 4A and Table 1) and, in agreement with a previous study [19], the resultant peak I Na was increased. The peak WT I Na was 16 T 4% larger at 42 -C compared to 22 -C; L325R I Na was increased by 24 T 8%.…”

Temperature dependence of human ether-à-go-go-related gene K+ currents

“…Despite there being numerous studies of the effects of temperature on the kinetics of ion channel gating, there are relatively few studies on the effect of temperature on steady-state activation and inactivation that we use for comparison with our results. Similar to the results reported here, increased temperature has been reported to result in depolarizing shifts in V 1/2 of inactivation for voltage-gated Na ϩ channels (35,40,44,48) and for C-type inactivation in Shaker K ϩ channels (29). Conversely, increased temperature results in only small shifts in V 1/2 of activation for Shaker K ϩ channels (43) and minimal shifts for Na ϩ channels (40,44,48).…”

Larger Cell Size in Rabbits With Heart Failure Increases Myocardial Conduction Velocity and QRS Duration

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