Temperature dependence of sodium current block by lidocaine in cardiac Purkinje cells

Cardiac Na current block by antiarrhythmic drugs has usually been studied at lower than physiological temperatures to achieve adequate voltage control, but the effect of temperature on block is not well characterized. Using a large suction pipette, we studied the effect of 50 microM lidocaine on blocking peak Na current between 10 and 25 degrees C in cells isolated from canine cardiac Purkinje fibers using three voltage clamp protocols: 1) development of block during a prolonged depolarization, 2) recovery from block after a prolonged depolarization, and 3) development of block during trains of depolarizations. At least two exponential components [a fast component with time constant (tau f) and relative amplitude (as) and a slow component with time constant (tau f) and relative amplitude (as)] were required to describe both development and recovery in lidocaine. For development of block between 10 and 25 degrees C, tau s decreased from 1,100 to 200 ms but tau f remained about the same (less than 30 ms), and as approximately equal to 0.8 and af approximately equal to 0.2 did not change with temperature. For recovery between 10 and 25 degrees C, tau a decreased from approximately 2,500 to 35 ms, tau f was relatively constant at approximately 25 ms, af decreased from 0.46 to 0.16, and as increased from 0.54 to 0.84. The fractional block developed during pulse trains decreased at higher temperatures (from 0.55 at 10 degrees C to 0.22 at 25 degrees C) and developed more quickly with time constant 6 pulses at 10 degrees C to 1.3 pulses at 25 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)