A1 adenosine receptor-mediated modulation of neuronal ATP-sensitive K channels in rat substantia nigra.
ATP-sensitive K (K(ATP)) channels, widely expressed in cytoplasmic membranes of neurons, couple cell metabolism to excitability. They are considered to play important roles in controlling seizure activity during hypoxia and in neuroprotection against cell damage during hypoxia, ischemia and excitotoxicity. It is known that adenosine augments the opening of cardiac surface K(ATP) channels by reducing the sensitivity of these channels to ATP blockade. We investigated whether a similar modulation occurs in neuronal channels. Whole cell voltage-clamp recordings were made using rat midbrain slices to record the membrane current and conductance in principal neurons of the substantia nigra pars compacta (SNc). When the pipette solution contained 1 mM ATP, the membrane current at -60 mV and cellular conductance remained stable for at least 15 min. When slices were treated with (-)-N(6)-2-phenylisopropyl adenosine (R-PIA), a selective agonist for A(1) adenosine receptors, in the same condition, the outward current developed slowly to the amplitude of 109.9+/-26.6 pA, and conductance increased to 229+/-50% of the baseline. These changes were strongly inhibited by 200 microM tolbutamide, a K(ATP) channel blocker, suggesting that opening of K(ATP) channels mediated these changes. Pretreatment with 8-cyclopentyltheophylline (CPT), a selective A(1) adenosine receptor antagonist, abolished the outward current and conductance increases. Treatment of adenosine resulted in the similar changes sensitive to tolbutamide. These changes were abolished by CPT. These results suggest that activation of A(1) adenosine receptors promotes the opening of K(ATP) channels in principal neurons of the SNc by removing the blockade by ATP.
Andoh
Tomio
T
Department of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama 236-0004, Japan. psdelico06@yahoo.co.jp
Ishiwa
Dai
D
Kamiya
Yoshinori
Y
Echigo
Noriyuki
N
Goto
Takahisa
T
Yamada
Yoshitsugu
Y
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D013378:Substantia Nigra / Q000166:cytology*; D014044:Tolbutamide / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D043682:Receptor, Adenosine A1; C047235:N-(1-methyl-2-phenylethyl)adenosine; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D000241:Adenosine