Effects of carvedilol on delayed rectifier and transient inactivating potassium currents in rat hippocampal CA1 neurons

The aims of the present study were to investigate the mechanism(s) underlying the protective effect of carvedilol against neural damage. 2. The transient inactivating potassium current (I(A) ) and the delayed rectifier potassium current (I(K) ) in rat hippocampal CA1 pyramidal neurons were recorded using whole-cell patch-clamp techniques. 3. Carvedilol (0.1-3 μmol/L) significantly inhibited I(K) with an IC(50) of 1.3 μmol/L and the inhibition was voltage independent. Over the same concentration range, carvedilol had no effect on the amplitude of I(A). At 1 μmol/L, carvedilol did not significantly change the steady state activation curves of I(A) and I(K), but did negatively shift their steady state inactivation curves. Recovery from inactivation was slowed for both I(A) and I(K). The inhibitory effect of carvedilol on I(K) was not affected by the adrenoceptor agonists phenylephrine and prazosin or the adrenoceptor antagonist isoproterenol, but propranolol was able to shift the dose-response curve of carvedilol for I(K) to the right. 4. Because I(K) is the main pathway for loss of intracellular potassium from depolarized neurons, selective obstruction of I(K) by carvedilol could be useful for neuroprotection.