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Blockade of Kv3.1 Channels by the Antidepressant Drug Citalopram

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We here investigated the interaction between citalopram, a selective serotonin reuptake inhibitor, and the cloning neuron rat Kv3.1 channel stably expressed in Chinese hamster ovarian cells using patch clamp techniques. As a result of the experiment, citalopram rapidly reduced the Kv3.1 ion current in a concentration-dependent and reversible manner (IC50 = 56.6 μM) and accelerated the rate of inactivation decay of Kv3.1 currents. The suppression of Kv3.1 current was detected over the whole voltage range in which Kv3.1 was activated. In the voltage range where the channel is fully activated, there is significant effect of voltage on the degree of inhibition. Citalopram slowed its deactivation process, resulting in a tail crossing. Citalopram-induced suppression of Kv3.1 showed no use dependence. Our results suggest that citalopram inhibits Kv3.1 currents while the channel is in the open state, implying that citalopram promotes the pro-convulsant effect on epilepsy through Kv3.1 inhibition, and indicate that there is a need for concern when using this drug in epilepsy patients with depression.

Abstract

We here investigated the interaction between citalopram, a selective serotonin reuptake inhibitor, and the cloning neuron rat Kv3.1 channel stably expressed in Chinese hamster ovarian cells using patch clamp techniques. As a result of the experiment, citalopram rapidly reduced the Kv3.1 ion current in a concentration-dependent and reversible manner (IC50 = 56.6 μM) and accelerated the rate of inactivation decay of Kv3.1 currents. The suppression of Kv3.1 current was detected over the whole voltage range in which Kv3.1 was activated. In the voltage range where the channel is fully activated, there is significant effect of voltage on the degree of inhibition. Citalopram slowed its deactivation process, resulting in a tail crossing. Citalopram-induced suppression of Kv3.1 showed no use dependence. Our results suggest that citalopram inhibits Kv3.1 currents while the channel is in the open state, implying that citalopram promotes the pro-convulsant effect on epilepsy through Kv3.1 inhibition, and indicate that there is a need for concern when using this drug in epilepsy patients with depression.

참고문헌 (53)

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