Effect of chronic hypoxia on ion channel development in cultured cardiac cells

In order to investigate mechanisms underlying the postnatal development of the transient outward current (Ito) in the rat heart, we established a primary culture of neonatal rat ventricular myocytes and studied the modulated expressions of Ito under normoxic (21% O2) and hypoxic (7.5% O2) growth conditions. During development from day 5 to day 15 in the normoxic cultures, Ito density doubled without any changes to the kinetics of current inactivation. Chronic hypoxia from day 6 to day 15 prevented this increase in Ito density. The reduced expression of Ito under hypoxic conditions was due to the loss of the fast inactivating component of Ito (Ito,f) These observations suggest that ion channels in neonatal rat cardiomyocytes in primary culture are not constitutively expressed but can be regulated by extrinsic factors. The postnatal increase in Ito density among newborn rats is closely associated with an alteration in oxygen tension.