The action of adrenaline on pace-maker activity in cardiac Purkinje fibres

1. Adrenaline is known to shift the activation curve for iK2 (s infinite curve) in a positive direction on the voltage axis. This should cause an increase in the slope of diastolic depolarization, but cannot account for the experimentally observed increase in the maximum diastolic potential (MDP). 2. On application of adrenaline, in voltage clamp studies on short sheep cardiac Purkinje fibres there is a consistent 5-15 mV negative shift of the reversal potential for the pace-maker current, iK2. This shift is not reversed on application of the beta-blockers sotalol or propranolol, or on washout for up to one hour. 3. A computer simulation, including this effect of adrenaline, shows that it can shift the maximum diastolic potential in the hyperpolarizing or depolarizing direction depending on the initial value of [K+]o. In both cases it will add to the increase in rate caused by the positive shift of the activation curve for iK2 (the s infinite shift). 4. Studies of the effects of adrenaline on the MDP and rate in long sheep Purkinje fibres show a slower reversibility of the MDP than the rate, consistent with a slower reversal of the shift in the iK2 reversal potential than the shift in s infinite. 5. Possible mechanisms of the shift in reversal potential are discussed with respect to K+ balance in the intercellular clefts of the Purkinje fibre, including a a stimulation of the Na+- K+ pump. The possible sources of voltage clamp artifact are also discussed.