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See text. 21 Cardiac Cellular Pharmacology 5 (+) o+---------------~~--------~~----------~-- 1m IO-Bamp 5 (-) 10 -100 -60 -80 -40 VminmV Figure 7. "Steady-state" current-voltage relationship iu a sheep Purkiuje fiber, where trausmembrane current is measured after long (10 sec) test voltage clamps. Note the marked decrease in membrane slope conductance at transmembrane voltages positive to -80 mY, with negative slope conductances for about 20 mV positive to -70 mV (so-called inward rectification).

When electrogenic pumping is activated, it provides outward current which opposes diastolic depolarization. Electrogenic sodium pumping has been proposed to explain such phenomena as hyperpolarization of Purkinje fibers by catecholamines and suppression of phase 4 depolarization in cardiac Purkinje fibers by rapid stimulation (see below). B. Inward Currents Inward current is a prerequisite for diastolic depolarization. Two inward currents will be discussed in this section: the background inward current which participates in slow diastolic depolarization and the rapid, inward sodium current which is responsible for the action potential upstroke.

The kinetic behavior of m and h is described by: dm -dt = (X m (1 - m) - f3 m m (18) (19) 32 Francis M. Weld and J. Thomas Bigger, Jr. 0 -100 -50 o mY -100 -50 o mY Figure l2A. Steady-state voltage dependence of the kinetic factors, m and h, for fast inward sodium conductance. These curves follow the values of m and h when the transmembrane voltage has been held constant for a long period of time. Note that the value of m 3 h, a major determinant of the magnitude of sodium conductance [equation (17)].

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