title: Feedback inhibition of action potential discharge by endogenous adenosine enhancement of the medium afterhyperpolarization.
abstract: Phasic activity in supraoptic nucleus vasopressin neurones is characterized by alternating periods of activity (bursts) and silence. During bursts, activation of a medium afterhyperpolarization induces spike frequency adaptation. Antagonism of A1 adenosine receptors within the supraoptic nucleus decreases spike frequency adaptation and prolongs phasic bursts in vivo, indicating that endogenous adenosine contributes to spike frequency adaptation. Here we used sharp electrode intracellular recordings from supraoptic nucleus neurones in hypothalamic explants to show that endogenous adenosine increases medium afterhyperpolarization amplitude to enhance spike frequency adaptation during phasic bursts. Superfusion of the A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT, 10 microM) increased intraburst firing rate of phasic neurones (by 2.0 +/- 0.7 spikes s(-1), P = 0.03) and burst duration (by 141 +/- 113 s, P = 0.03). The CPT-induced increase in intraburst firing rate developed over the first few seconds of firing and persisted thereafter. In a separate series of experiments, CPT reduced the amplitude of the medium afterhyperpolarization evoked by a 1 s 20 Hz spike train (by 0.8 +/- 0.3 mV, P < 0.001) in supraoptic nucleus neurones; this inhibition was not prevented by 3 mM CsCl (0.8 +/- 0.1 mV decrease, P < 0.01) to block the afterdepolarization (which overlaps temporally with the medium afterhyperpolarization). In the presence of apamin to block the medium afterhyperpolarization, CPT did not alter afterdepolarization amplitude. Taken together, these data show that endogenous adenosine enhances medium afterhyperpolarization amplitude to contribute to spike frequency adaptation in phasic supraoptic nucleus neurones.
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Ming
authors.initials: M
authors.lastname: Ruan
authors.forename: Colin H
authors.initials: CH
authors.lastname: Brown
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000241:Adenosine / Q000502:physiology*; D000818:Animals; D025461:Feedback, Physiological / Q000502:physiology*; D005260:Female; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000502:physiology
chemical_list: D000241:Adenosine