scholarly journals ATP-sensitive K+ channel modification by metabolic inhibition in isolated guinea-pig ventricular myocytes.

1993 ◽  
Vol 465 (1) ◽  
pp. 163-179 ◽  
Author(s):  
N Deutsch ◽  
J N Weiss
2001 ◽  
Vol 101 (3) ◽  
pp. 243-251 ◽  
Author(s):  
Hiroshi SATOH ◽  
Shiho SUGIYAMA ◽  
Noriyuki NOMURA ◽  
Hajime TERADA ◽  
Hideharu HAYASHI

The increase in the intracellular Na+ concentration ([Na+]i) during myocardial ischaemia is crucial for ischaemia/reperfusion cell injury, and the cardiac subtype of the Na+/H+ exchanger (NHE-1) has been shown to be a major pathway for Na+ loading. While the importance of glycolytically derived ATP for the optimal functioning of membrane transporters and channels has been suggested, whether NHE-1 is actually activated during myocardial ischaemia remains controversial. Here we examined whether the activity of NHE-1 is predominantly dependent on intracellular ATP generated by glycolysis, and whether the additional inhibition of glycolysis can affect the increase in [Na+]i during the inhibition of oxidative phosphorylation in intact guinea pig ventricular myocytes. The selective inhibition of glycolysis by 2-deoxyglucose prevented the recovery of intracellular pH and the transient increase in [Na+]i following intracellular acidosis induced by a NH4Cl pre-pulse. During severe metabolic inhibition (SMI; induced by amobarbital and carbonyl cyanide m-chlorophenylhydrazone in a glucose-free perfusate), most myocytes changed from rod-shaped to contracted forms by ~ 15 min. [Na+]i increased linearly until rigor contracture occurred, but after rigor contracture the rate of increase was blunted. The increase in [Na+]i during SMI was suppressed significantly by an inhibitor of NHE-1, hexamethylene amiloride. The increase in the intracellular Mg2+ concentration, which can reciprocally indicate depletion of intracellular ATP, was small during the initial 10 min of SMI, but became larger from just a few minutes before rigor contracture. In the presence of 2-deoxyglucose, the time to rigor during SMI was shortened, but the increase in [Na+]i before rigor contracture was not significant, and was much less than that in the absence of 2-deoxyglucose. It is concluded that ATP generated by glycolysis is essential to activate NHE-1, and that the dependence of NHE-1 on glycolysis might affect the increase in [Na+]i observed during myocardial ischaemia.


1992 ◽  
Vol 220 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Tatsuto Notsu ◽  
Kiyokazu Ohhashi ◽  
Isao Tanaka ◽  
Hiroshi Ishikawa ◽  
Takeshi Niho ◽  
...  

1995 ◽  
Vol 268 (3) ◽  
pp. H1045-H1052 ◽  
Author(s):  
S. Seki ◽  
K. T. MacLeod

Single, enzymatically isolated guinea pig ventricular myocytes were exposed to 3-min periods of anoxia with glucose-free Tyrode solution containing 1 mM sodium dithionite (Na2S2O4) and were then reoxygenated for 10 min. The myocytes were exposed to rapid applications of 10 mM caffeine during the control, anoxic, and reoxygenation periods. Intracellular Ca2+ concentration ([Ca2+]i) was measured ratiometrically using indo 1 with simultaneous measurements of cell length. The effects of anoxia on Ca2+ were compared with those of hypoxia and metabolic inhibition. The amplitude of the electrically stimulated (Ca transient) and caffeine-evoked Ca2+ (Caff-Ca) transients decreased during anoxia and recovered after reoxygenation. Diastolic [Ca2+]i did not change during 3 min of anoxia but rose progressively after prolonged anoxia and remained at this higher level on reoxygenation. During metabolic inhibition the Ca transients decreased, while the Caff-Ca transients showed no change in amplitude. During hypoxia the Ca transients decreased. Anoxia slowed the time to peak of the Ca transient, the time to 50% relaxation, and the time to 90% relaxation. The decline of indo 1 fluorescence on rapid caffeine application was slowed during anoxia, metabolic inhibition, and hypoxia and partially recovered after reoxygenation.


1990 ◽  
Vol 259 (5) ◽  
pp. H1448-H1454 ◽  
Author(s):  
R. W. Hadley ◽  
J. R. Hume

Currents through time-dependent K+ channels (also referred to as IK or the delayed rectifier) were studied with the whole cell patch-clamp technique in isolated guinea pig ventricular myocytes. IK measurements were restricted to the examination of deactivation tail currents. Substitution of various monovalent cations for external K+ produced shifts of the reversal potential of IK. These shifts were used to calculate permeability ratios relative to K+. The permeability sequence for the IK channels was K+ = Rb+ greater than NH4+ = Cs+ greater than Na+. Time-dependent outward currents were also examined when the myocytes were dialyzed with Cs+ instead of K+. A sizeable time-dependent outward current, quite similar to that seen with K+ dialysis, was demonstrated. This current was primarily carried by intracellular Cs+, as the reversal potential of the current shifted 46 mV per 10-fold change of external Cs+ concentration. The significance of Cs+ permeation through IK channels is discussed with respect to the common use of Cs+ in isolating other currents.


1994 ◽  
Vol 479 (1) ◽  
pp. 95-107 ◽  
Author(s):  
T Furukawa ◽  
L Virág ◽  
N Furukawa ◽  
T Sawanobori ◽  
M Hiraoka

1991 ◽  
Vol 103 (3) ◽  
pp. 1641-1648 ◽  
Author(s):  
Keiko Nakayama ◽  
Zheng Fan ◽  
Fumiaki Marumo ◽  
Tohru Sawanobori ◽  
Masayasu Hiraoka

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