ADENOSINE DECREASES ACTION-POTENTIAL DURATION BY MODULATION OF A-CURRENT IN RAT LOCUS-COERULEUS NEURONS

The possibility that adenosine modulates voltage-dependent conductance s in locus coeruleus neurons was investigated in current-clamp and vol tage-clamp experiments in a totally submerged rat brain slice preparat ion. Adenosine (100 mu M) reduced the duration of control action poten tials and action potentials prolonged by 1 mM barium. Adenosine (100 m u M) also reduced the amplitude and slightly reduced the duration of T TX-resistant ''calcium'' action potentials. Action potential duration was also reduced by the adenosine receptor agonist 2-chloroadenosine i n a concentration-dependent manner and the adenosine-induced reduction of action potential duration was blocked by the adenosine receptor an tagonist 8-(p-sulfophenyl)theophylline, indicating that this action of adenosine is mediated by an adenosine receptor. The adenosine-induced reduction of action potential duration persisted in the presence of e xternally applied tetraethylammonium ion (6 mM) and cesium (3 mM). By contrast, adenosine did not reduce the duration of the action potentia l in the presence of 500 mu M 4-aminopyridine (4-AP). Furthermore, 4-A P (30 mu M) blocked the adenosine-induced reduction of action potentia l duration recorded in the presence of 1 mM barium. These data suggest ed that adenosine may be acting on the voltage-dependent, 4-AP-sensiti ve potassium current, I-A. Single-electrode voltage clamp was used to study I-A directly. I-A was activated by depolarizing voltage pulses f rom a hyperpolarized holding potential and was blocked by 1 mM 4-AP. A denosine (300 mu M) enhanced I-A by shifting the steady-state inactiva tion curve in the depolarizing direction. The mean shift of the curve at 80% inactivation was 4.6 mV, which increases the amount of I-A avai lable for activation at the threshold potential by 2.5-fold. The same concentration of 4-AP (30 mu M) that blocked the adenosine-induced red uction in spike duration, completely blocked I-A evoked from threshold potential. These data suggest that adenosine reduces action potential duration of locus coeruleus neurons through enhancement of I-A.