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

P>1. 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 mu mol/L) significantly inhibited I-K with an IC50 of 1.3 mu mol/L and the inhibition was voltage independent. Over the same concentration range, carvedilol had no effect on the amplitude of I-A. At 1 mu mol/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.