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

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 μmol/L) significantly inhibited I_K with an IC₅₀ 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.