2020YAKUGAKU ZASSHIOpen access

Role of T-type Calcium Channels in Regulating Neuronal Function

Yasushi Yabuki

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Abstract

T-type calcium channels are low-threshold voltage-gated calcium channel and characterized by unique electrophysiological properties such as fast inactivation and slow deactivation kinetics. All subtypes of T-type calcium channel (Cav3.1, 3.2 and 3.3) are widely expressed in the central nerve system, and they have an important role in homeostasis of sleep, pain response, and development of epilepsy. Recently, several reports suggest that T-type calcium channels may mediate neuronal plasticity in the mouse brain. We succeeded to develop T-type calcium channel enhancer ethyl 8'-methyl-2',4-dioxo-2-(piperidin-1-yl)-2'H-spiro[cyclopentane-1,3'-imidazo[1,2-a]pyridine]-2-ene-3-carboxylate (SAK3) which enhances Cav3.1 and 3.3 currents in each-channel expressed neuro2A cells. SAK3 can promote acetylcholine (ACh) release in the mouse hippocampus via enhancing T-type calcium channel. In this review, we have introduced the role of T-type calcium channel, especially Cav3.1 channel in the mouse hippocampus based on our previous data using SAK3 and Cav3.1 knockout mice.

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T-type calcium channels are low-threshold voltage-gated calcium channel and characterized by unique electrophysiological properties such as fast inactivation and slow deactivation kinetics. All subtypes of T-type calcium channel (Cav3.1, 3.2 and 3.3) are widely expressed in the central nerve system, and they have an important role in homeostasis of sleep, pain response, and development of epilepsy. Recently, several reports suggest that T-type calcium channels may mediate neuronal plasticity in the mouse brain. We succeeded to develop T-type calcium channel enhancer ethyl 8'-methyl-2',4-dioxo-2-(piperidin-1-yl)-2'H-spiro[cyclopentane-1,3'-imidazo[1,2-a]pyridine]-2-ene-3-carboxylate (SAK3) which enhances Cav3.1 and 3.3 currents in each-channel expressed neuro2A cells. SAK3 can promote acetylcholine (ACh) release in the mouse hippocampus via enhancing T-type calcium channel. In this review, we have introduced the role of T-type calcium channel, especially Cav3.1 channel in the mouse hippocampus based on our previous data using SAK3 and Cav3.1 knockout mice.

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Available abstract

T-type calcium channels are low-threshold voltage-gated calcium channel and characterized by unique electrophysiological properties such as fast inactivation and slow deactivation kinetics. All subtypes of T-type calcium channel (Cav3.1, 3.2 and 3.3) are widely expressed in the central nerve system, and they have an important role in homeostasis of sleep, pain response, and development of epilepsy. Recently, several reports suggest that T-type calcium channels may mediate neuronal plasticity in the mouse brain. We succeeded to develop T-type calcium channel enhancer ethyl 8'-methyl-2',4-dioxo-2-(piperidin-1-yl)-2'H-spiro[cyclopentane-1,3'-imidazo[1,2-a]pyridine]-2-ene-3-carboxylate (SAK3) which enhances Cav3.1 and 3.3 currents in each-channel expressed neuro2A cells. SAK3 can promote acetylcholine (ACh) release in the mouse hippocampus via enhancing T-type calcium channel. In this review, we have introduced the role of T-type calcium channel, especially Cav3.1 channel in the mouse hippocampus based on our previous data using SAK3 and Cav3.1 knockout mice.

Key concepts: T-type calcium channel, P-type calcium channel, Calcium channel, Voltage-dependent calcium channel, N-type calcium channel, Chemistry, R-type calcium channel, L-type calcium channel

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