Ischemia alters the electrical activity of pacemaker cells isolated from the rabbit sinoatrial node.
The purpose of this study was to investigate the mechanisms responsible for ischemia-induced changes in spontaneous electrical activity. An ischemic-like Tyrode solution (pH 6.6) reversibly depolarized the maximum diastolic potential (MDP) and reduced the action potential (AP) overshoot (OS). We used SNARF-1, which is an indicator of intracellular pH (pH(i)), and perforated-patch techniques to test the hypothesis that acidosis caused these effects. Acidic but otherwise normal Tyrode solution (pH 6.8) produced similar effects. Basic Tyrode solution (pH 8.5) hyperpolarized the MDP, shortened the AP, and slowed the firing rate. In the presence of "ischemic" Tyrode solution, hyperpolarizing current restored the MDP and OS to control values. HOE-642, an inhibitor of Na/H exchange, did not alter pH(i) or electrical activity and did not prevent the effects of ischemic Tyrode solution or recovery after washout. Time-independent net inward current but not hyperpolarization-activated inward current was enhanced by ischemic Tyrode solution or by 30 microM BaCl(2), a selective blocker of inward-rectifying K currents at this concentration. The results suggest that 1) acidosis was responsible for the ischemia-induced effects but Na/H exchange was not involved, 2) the OS was reduced because of depolarization-induced inactivation of inward currents that generate the AP upstroke, and 3) reduction of an inward-rectifying outward K current contributed to the depolarization.
Gryshchenko
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Department of Physiology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.
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Nathan
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D000200:Action Potentials; D000818:Animals; D001578:Benzopyrans; D002469:Cell Separation; D002478:Cells, Cultured; D004553:Electric Conductivity; D004594:Electrophysiology; D005456:Fluorescent Dyes; D006146:Guanidines / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000502:physiology; D008297:Male; D008564:Membrane Potentials; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009284:Naphthols; D018408:Patch-Clamp Techniques / Q000379:methods; D011817:Rabbits; D012235:Rhodamines; D012849:Sinoatrial Node / Q000166:cytology* / Q000503:physiopathology*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology
D001578:Benzopyrans; D005456:Fluorescent Dyes; D006146:Guanidines; D007473:Ion Channels; D009284:Naphthols; D012235:Rhodamines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C091666:seminaphthorhodaminefluoride; C093373:cariporide