The calmodulin inhibitor and antipsychotic drug Trifluoperazine (cas 117-89-5) inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells
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Add time:09/03/2019 Source:sciencedirect.com
We investigated the effect of the calmodulin inhibitor and antipsychotic drug Trifluoperazine (cas 117-89-5) on voltage-dependent K+ (Kv) channels. Kv currents were recorded by whole-cell configuration of patch clamp in freshly isolated rabbit coronary arterial smooth muscle cells. The amplitudes of Kv currents were reduced by trifluoperazine in a concentration-dependent manner, with an apparent IC50 value of 1.58 ± 0.48 μM. The rate constants of association and dissociation by trifluoperazine were 3.73 ± 0.33 μM−1 s−1 and 5.84 ± 1.41 s−1, respectively. Application of trifluoperazine caused a positive shift in the activation curve but had no significant effect on the inactivation curve. Furthermore, trifluoperazine provoked use-dependent inhibition of the Kv current under train pulses (1 or 2 Hz). These findings suggest that trifluoperazine interacts with Kv current in a closed state and inhibits Kv current in the open state in a time- and use-dependent manner, regardless of its function as a calmodulin inhibitor and antipsychotic drug.
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