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Effects of carvedilol on delayed rectifier and transient inactivating potassium currents in rat hippocampal CA1 neurons
Author(s) -
Duan JingJing,
Wang Qin,
Deng ChunYu,
Kuang SuJuan,
Chen RuZhu,
Tao Liang
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2010.05427.x
Subject(s) - carvedilol , phenylephrine , chemistry , prazosin , antagonist , potassium , patch clamp , biophysics , propranolol , cardiac transient outward potassium current , potassium channel , medicine , pharmacology , endocrinology , biochemistry , receptor , biology , heart failure , organic chemistry , blood pressure
Summary 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 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.