BACKGROUND K+ CURRENTS AND RESPONSE TO METABOLIC INHIBITION DURING EARLY DEVELOPMENT IN RAT CARDIOCYTES

The effects of metabolic inhibition on K+ background currents and acti on potential duration were investigated in neonatal rat ventricle cell s during early development. Action potentials and ionic currents were measured with the patch clamp technique in current and voltage clamp m ode 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 mu m(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 mu M 2,4 DN P) 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,I-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 i n slope conductance when [K](o) was raised. Inward rectification was a bolished by 2.4 mM Ba2+ in 1 day old cells and by 0.2 mM one week afte r birth; (2) a glibenclamide (100 mu M) sensitive component that devel oped with time after membrane rupture (5-10 min) showing a higher curr ent density in 7 than in 1 day old animals (1.4 vs 0.2 mu A.cm(-2) at -50 mV); and (3) a small and almost linear leak component of comparabl e amplitude in both age groups. Inhibition of oxidative phosphorylatio n with 2.5 mu M carbonylcyanide m-chlorophenylhydrazone induced the de velopment of background currents with different properties in both age groups: An inwardly rectifying Ba2+ sensitive current in 1 day old ce lls and a glibenclamide sensitive outwardly rectifying current in the 7 day old group. In contrast, exposure to 5 mM 2-DG provoked in all ce lls the development of an outwardly rectifying current that was blocke d by glibenclamide. We conclude that the electrophysiologic response t o metabolic inhibition is determined by the relative importance of the metabolic pathways present which in turn depends on the developmental state of the cells.