Carvedilol acts as an open- and state-dependent blocker of delayed rectifying K+ channels in neuronal cells, independent of its antioxidative effects.
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Carvedilol may modulate neuronal excitability via K+ channel blockade; leaves open its contribution to clinical effects in patients.
The effects of the β‐adrenoceptor antagonist carvedilol on delayed rectifier K + current ( I K (DR) ) were examined in NG108‐15 neuronal cells. Carvedilol (1–100µM) reversibly blocked I K (DR) with an IC 50 value of 5 µM. I K (DR) in response to depolarizing pulses was sensitive to inhibition by quinidine or dendrotoxin, but not by iberiotoxin, 5‐hydroxydecanoate sodium, or linopiridine. The carvedilol‐induced inhibition of I K (DR) could not be reversed by further application of t ‐butyl hydroperoxide or diazoxide. The inhibition of I K (DR) by carvedilol could still be observed in cells preincubated with t ‐butyl hydroperoxide (1 mM), ruthenium red (30 µM), or carbonyl cyanide m ‐chlorophenyl hydrazone (10 µM). The presence of carvedilol enhanced both the rate and extent of I K (DR) inactivation. Recovery from block by carvedilol (3 µM) could be fitted by a single exponential with a value of 1.64 s. Crossover of tail currents in the presence of carvedilol was also observed. Cell‐attached single‐channel recordings revealed that carvedilol suppressed channel activity without altering single‐channel amplitude. With the aid of the binding scheme, a quantitative description of the carvedilol actions on I K (DR) was also developed that clearly showed that in addition to being an antioxidative agent, carvedilol can block delayed rectifying K + channel of neurons in an open‐ and state‐dependent manner. Drug Dev. Res. 58:196–208, 2003.
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Liu et al. (2003) studied this question.
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