ELECTROPHYSIOLOGICAL ACTIONS OF ADENOSINE AND AMINOPHYLLINE IN SPONTANEOUSLY BEATING AND VOLTAGE-CLAMPED RABBIT SINOATRIAL NODE PREPARATIONS

Effects of adenosine (30 to 200 mumol/l) on the spontaneous action potentials and the membrane currents in rabbit sino-atrial node (SA) preparations were examined. Adenosine (30 mumol/l) lengthened the action potential duration and the cycle length. At 100 mumol/l, adenosine also hyperpolarized the maximum diastolic potential. However, the action potential amplitude and the maximum rate of depolarization V(max)) were unaffected. In the presence of adenosine (200 mumol/l), addition of aminophylline (an antagonist) (23 - 46 mumol/l) shortened the cycle length and depolarized the maximum diastolic potential to the contrary. Aminophylline did not antagonize the prolongation of the action potential. Aminophylline (46 mumol/l) alone decreased the cycle length and the maximum diastolic potential, but did not affect the action potential amplitude, the action potential duration and the V(max). In the presence of aminophylline (46 mumol/l), addition of adenosine (200 mumol/l) increased the cycle length and the action potential duration, and decreased V(max). In voltage-clamp experiments, adenosine greatly shifted the background current in the outward direction. Holding potential was -40 mV. Adenosine reduced a slow inward and a time-dependent outward current, in a concentration-dependent manner. Adenosine did not affect the time constant of inactivation phase and the voltages of the half-maximum activation and inactivation for the slow inward current. The activation curve for the outward current was also unaffected. A hyperpolarization-activated inward current was decreased. In the presence of aminophylline (46 mumol/l), adenosine (200 mumol/l) decreased the slow inward current, the time-dependent outward current and the hyperpolarization-activated inward current. These results suggest that adenosine produces its actions on the heart by inhibition of ionic currents and activation of the outward background current.