Effects of carvedilol on delayed rectifier and transient inactivating potassium currents in rat hippocampal CA1 neurons |
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Authors: | Jing‐Jing Duan Qin Wang Chun‐Yu Deng Su‐Juan Kuang Ru‐Zhu Chen Liang Tao |
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Affiliation: | 1. Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‐Sen University;2. These authors contributed equally to this study.;3. Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China |
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Abstract: | 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 (IA) and the delayed rectifier potassium current (IK) in rat hippocampal CA1 pyramidal neurons were recorded using whole‐cell patch‐clamp techniques. 3. Carvedilol (0.1–3 μmol/L) significantly inhibited IK 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 IA. At 1 μmol/L, carvedilol did not significantly change the steady state activation curves of IA and IK, but did negatively shift their steady state inactivation curves. Recovery from inactivation was slowed for both IA and IK. The inhibitory effect of carvedilol on IK 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 IK to the right. 4. Because IK is the main pathway for loss of intracellular potassium from depolarized neurons, selective obstruction of IK by carvedilol could be useful for neuroprotection. |
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Keywords: | CA1 pyramidal neurons carvedilol delayed rectifier potassium current (IK) transient inactivating potassium current (IA) |
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