Endogenous adenosine and ATP-sensitive potassium channel modulate anoxia-induced electrophysiological changes of pacemaker cells in sinoatrial node of guinea pigs.
OBJECTIVE
To investigate the electrophysiological effects of adenosine deaminase (ADase, an enzyme converting adenosine to inosine and ammonia), 8-phenyltheophylline (8-PT, a nonselective antagonist of adenosine receptors) and glibenclamide (Gli, a potent blocker of ATP-sensitive K+ channels) on anoxic pacemaker cells of SA node.


METHODS
Anoxia of pacemaker cells in SA node of guinea-pig was induced by perfused for 20 min with a modified K-H solution gassed with 100% N2 deprived of glucose. Parameters of action potentials including maximal diastolic potential (MDP), amplitude of action potential (APA), duration of 90% repolarization (APD90), maximal rate of depolarization (Vmax), rate of pacemaker firing (RPF), and velocity of diastolic (phase 4) depolarization (VDD) were recorded using intracellular microelectrodes.


RESULTS
Anoxia increased MDP, APA, and Vmax and decreased VDD, RPF in a time-dependent manner. ADase 10 U.L-1, 8-PT 0.1 mumol.L-1 and Gli 10 mumol.L-1 significantly attenuated the electrophysiological changes of pacemaker cells in sincatrial node induced by anoxia.


CONCLUSIONS
Endogenous adenosine and ATP-sensitive K+ channels may play an important role in the generation of anoxic bradycardia in guinea pigs.
Li
Y L
YL
Department of Physiology, Hebei Medical College, Shijiazhuang, China.
He
R R
RR
D000200:Action Potentials / Q000187:drug effects; D000243:Adenosine Deaminase / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D015687:Cell Hypoxia; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012849:Sinoatrial Node / Q000166:cytology / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D000243:Adenosine Deaminase; D005905:Glyburide