Adenosine decreases action potential duration by modulation of A- current in rat locus coeruleus neurons

Abstract

The possibility that adenosine modulates voltage-dependent conductances in locus coeruleus neurons was investigated in current-clamp and voltage-clamp experiments in a totally submerged rat brain slice preparation. Adenosine (100 microM) reduced the duration of control action potentials and action potentials prolonged by 1 mM barium. Adenosine (100 microM) also reduced the amplitude and slightly reduced the duration of TTX-resistant "calcium" action potentials. Action potential duration was also reduced by the adenosine receptor agonist 2-chloroadenosine in a concentration-dependent manner and the adenosine-induced reduction of action potential duration was blocked by the adenosine receptor antagonist 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 externally applied tetraethylammonium ion (6 mM) and cesium (3 mM). By contrast, adenosine did not reduce the duration of the action potential in the presence of 500 microM 4-aminopyridine (4-AP). Furthermore, 4-AP (30 microM) blocked the adenosine-induced reduction of action potential duration recorded in the presence of 1 mM barium. These data suggested that adenosine may be acting on the voltage-dependent, 4-AP-sensitive potassium current, IA. Single-electrode voltage clamp was used to study IA directly. IA was activated by depolarizing voltage pulses from a hyperpolarized holding potential and was blocked by 1 mM 4-AP. Adenosine (300 microM) enhanced IA by shifting the steady-state inactivation curve in the depolarizing direction.(ABSTRACT TRUNCATED AT 250 WORDS)