HYPOXIA INCREASES PERSISTENT SODIUM CURRENT IN RAT VENTRICULAR MYOCYTES

1. A persistent inward current activated by depolarization was recorde d using the whole-cell, tight seal technique in rat isolated cardiac m yocytes. The amplitude of the inward current increased when cells were exposed to a solution with low oxygen tension. 2. The persistent inwa rd current had the characteristics of the persistent Na+ current descr ibed previously in rat ventricular myocytes: it was activated at negat ive potentials (-70 mV), reversed close to the equilibrium potential f or Na+ (E(Na)), was blocked by TTX and was resistant to inactivation. 3. Persistent single Na+ channel currents activated by long (200-400 m s) depolarizations were recorded in cell-attached patches on isolated ventricular myocytes. Hypoxia increased the frequency of opening of th e persistent Na+ channels. 4. Persistent Na+ channels recorded during hypoxia had characteristics similar to those of persistent Na+ channel s recorded at normal oxygen tensions. They had a null potential at E(N a), their amplitude varied with [Na+], they were resistant to inactiva tion and their mean open time increased with increasing depolarization . 5. The persistent Naf channels in cell-attached patches were blocked by TTX (50 mu M) in the patch pipette and by lidocaine (100 mu M). 6. It was concluded that hypoxia increases the open probability of TTX-s ensitive, inactivation-resistant Na+ channels. The voltage dependence of these channels, and their greatly increased activity during hypoxia , suggest that they may play an important role in the generation of ar rhythmias during hypoxia.