Hypoxia inhibits the changes in action potentials and ion channels during primary culture of neonatal rat ventricular myocytes

Action potentials of rat ventricular myocytes are progressively shortened a fter birth within several weeks mainly due to a progressive increase in tra nsient outward potassium current (I-to). On the supposition that an elevati on in blood oxygen after birth may contribute to such developmental change, we studied effects of long-term exposure to hypoxia on changes in cardiac action potentials and I-to. Single ventricular myocytes isolated from day-o ld neonatal rat hearts were cultured in normoxic condition (21% O-2) for 15 days and served as control. To test the influence of long-term exposure to hypoxia. O-2 tension was reduced to 7.5% at day 6 during culture. In 15-da y cells cultured in normoxia. action potential duration (APD) was shortened by 44% (n = 11) compared with 5-day cells (n = 10); cell capacitance was i ncreased to 2.0-fold. I-to density was increased by 189-265% (n = 11) at vo ltage levels from -20 to 50 mV without any changes in the kinetics of curre nt inactivation. In 15-day cells cultured in hypoxia. APD was shortened onl y by 16% (n = 6) from control; the increment of cell capacitance was 2.1-fo ld (n = 6). The I-to increment was limited to 53% (n = 8); both inactivatio n and its recovery of the current was apparently slow-ed due to the amplifi cation of the slower component. These results suggest that the developmenta l augmentation of I-to expression during culture requires oxygen and the in crease in I-to and cell hypertrophy are likely regulated independently. (C) 1999 Academic Press.