Endogenous adenosine and ATP-sensitive potassium channel modulate anoxia-induced electrophysiological changes of pacemaker cells in sinoatrial node of guinea pigs
Abstract
AIM: 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.
CONCLUSION: Endogenous adenosine and ATP-sensitive K+ channels may play an important role in the generation of anoxic bradycardia in guinea pigs.
Keywords:
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.
CONCLUSION: Endogenous adenosine and ATP-sensitive K+ channels may play an important role in the generation of anoxic bradycardia in guinea pigs.