The effect of inhibition of mitochondrial energy metabolism on the transient inward current of isolated guinea-pig ventricular myocytes
| Autor: | Geert Callewaert, Edward Carmeliet, G Biermans, L H Opie, Johan Vereecke, William A. Coetzee |
|---|---|
| Rok vydání: | 1988 |
| Předmět: |
medicine.medical_specialty
Voltage clamp Guinea Pigs chemistry.chemical_element Action Potentials Calcium Ion Channels Mitochondria Heart chemistry.chemical_compound Adenosine Triphosphate Internal medicine medicine Myocyte Animals Molecular Biology Ion channel Endoplasmic reticulum Myocardium Depolarization Sarcoplasmic Reticulum Endocrinology chemistry Biophysics Potassium Cardiology and Cardiovascular Medicine Adenosine triphosphate Intracellular |
| Zdroj: | Journal of molecular and cellular cardiology. 20(3) |
| ISSN: | 0022-2828 |
| Popis: | Delayed afterdepolarizations (DADs) might underlie ischemic or reperfusion arrhythmias ( Ferrier et al. , 1985 ; Coetzee and Opie, 1987 ). These DADs are the result of a transient inward current i ti , which is caused by instability of the intracellular level of free Ca 2+ ( Ca i ) due to an oscillatory release of Ca from the sarcoplasmic reticulum ( Kass et al. , 1978 ). DADS are known to be abolished by hypoxia and by metabolic inhibition (Di Gennaro et al. , 1987; Coetzee and Opie, 1987 ), which could be caused by a number of different mechanisms: o (1) The large increase of potassium conductance associated with metabolic inhibition ( Vleugels et al. , 1980 ; Isenberg et al. , 1983 ) could prevent i ti from causing a marked depolarization, and would thus “mask” the DADS. (2) Although metabolic inhibition will eventually result in an increase of Ca i , a temporary decrease could initially take place, thereby minimizing the Ca instability. Two mechanisms are known which might produce such an effect: Firstly, the shortening of the action potential which occurs during metabolic inhibition will markedly reduce the time during which Ca channels remain open, theraby causing a diminished total Ca influx during the action potential ( Isenberg et al. , 1983 ; Noma and Shibasaki, 1985 ; Kakei et al. , 1985 ). Secondly, a direct reduction of i Ca by a decrease in ATP concentration, described by Irisawa and Kokubun (1983) , could also contribute to a decreased Ca load. (3) Metabolic inhibitors could possibly interfere with the cycling of Ca between different compartments within the cell, thereby altering the temporal variation in Ca i , and thus influencing i ti . (4) The inhibition of the DADs could be due to direct metabolic effects on the channels or carriers responsible for i ti . In this study, the mechanism of the inhibition of the DADs by metabolic inhibition was investigated in guinea-pig ventricular myocytes under voltage clamp conditions. Our data indicate that the blocking effect of metabolic inhibition on DADs cannot be explained solely as secondary to changes in K or Ca current. We show that ATP depletion by itself blocks i ti , probably by interfering with the Ca uptake of the sarcoplasmic reticulum, although a direct effect on the transport mechanism for i ti cannot be excluded. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|