Hypoxia Inhibits the Changes in Action Potentials and Ion Channels during Primary Culture of Neonatal Rat Ventricular Myocytes

Abstract

Action potentials of rat ventricular myocytes are progressively shortened after birth within several weeks mainly due to a progressive increase in transient outward potassium current (Ito). On the supposition that an elevation 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 Ito. Single ventricular myocytes isolated from day-old neonatal rat hearts were cultured in normoxic condition (21% O2) for 15 days and served as control. To test the influence of long-term exposure to hypoxia, O2tension was reduced to 7.5% at day 6 during culture. In 15-day cells cultured in normoxia, action potential duration (APD) was shortened by 44% (n=11) compared with 5-day cells (n=10); cell capacitance was increased to 2.0-fold. Itodensity was increased by 189–265% (n=11) at voltage levels from −20 to 50 mV without any changes in the kinetics of current inactivation. In 15-day cells cultured in hypoxia, APD was shortened only by 16% (n=6) from control; the increment of cell capacitance was 2.1-fold (n=6). The Itoincrement was limited to 53% (n=8); both inactivation and its recovery of the current was apparently slowed due to the amplification of the slower component. These results suggest that the developmental augmentation of Itoexpression during culture requires oxygen and the increase in Itoand cell hypertrophy are likely regulated independently.