Background K + currents and response to metabolic inhibition during early development in rat cardiocytes
Molecular and cellular biochemistry(1997)
Abstract
The effects of metabolic inhibition on K + background currents and action potential duration were investigated in neonatal rat ventricle cells during early development. Action potentials and ionic currents were measured with the patch clamp technique in current and voltage clamp mode in cells isolated with collagenase from 1 day and 7 day old rats. During the first postnatal week, the cell surface increased from 1700 to 2210 µm 2 and the membrane hyperpolarized from -66.1 to -72.0 mV. Concomitantly the action potential shortened and the plateau became more negative. Inhibition of oxidative phosphorylation (50 µM 2,4 DNP) or of glycolysis in 1 day old rats (5 mM 2-deoxyglucose, 2-DG) also shortened the action potential by about 50% after 5 min exposure. The background current measured in the absence of I Na , I Ca,L , and I to included: (1) an inward rectifying component whose I/V curves crossed over when measured in 6, 15, or 30 mM [K] o and showed an increase in slope conductance when [K] o was raised. Inward rectification was abolished by 2.4 mM Ba 2+ in 1 day old cells and by 0.2 mM one week after birth; (2) a glibenclamide (100 µM) sensitive component that developed with time after membrane rupture (5-10 min) showing a higher current density in 7 than in 1 day old animals (1.4 vs 0.2 µA · cm -2 at -50 mV); and (3) a small and almost linear leak component of comparable amplitude in both age groups. Inhibition of oxidative phosphorylation with 2.5 µM carbonylcyanide m-chlorophenylhydrazone induced the development of background currents with different properties in both age groups: An inwardly rectifying Ba 2+ sensitive current in 1 day old cells and a glibenclamide sensitive outwardly rectifying current in the 7 day old group. In contrast, exposure to 5 mM 2-DG provoked in all cells the development of an outwardly rectifying current that was blocked by glibenclamide. We conclude that the electrophysiologic response to metabolic inhibition is determined by the relative importance of the metabolic pathways present which in turn depends on the developmental state of the cells.
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Key words
neonatal rat ventricle cells,action potential duration,K+ background currents,metabolic inhibition,development
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