Voltage-Sensitive Calcium Channels in the Brain: Relevance to Alcohol Intoxication and Withdrawal

Voltage-sensitive Ca²⁺ (Ca_V) channels are the primary route of depolarization-induced Ca²⁺ entry in neurons and other excitable cells, leading to an increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i). The resulting increase in [Ca²⁺]_i activates a wide range of Ca²⁺-dependent processes in neurons, including neurotransmitter release, gene transcription, activation of Ca²⁺-dependent enzymes, and activation of certain K⁺ channels and chloride channels. In addition to their key roles under physiological conditions, Ca_V channels are also an important target of alcohol, and alcohol-induced changes in Ca²⁺ signaling can disturb neuronal homeostasis, Ca²⁺-mediated gene transcription, and the function of neuronal circuits, leading to various neurological and/or neuropsychiatric symptoms and disorders, including alcohol withdrawal induced-seizures and alcoholism.