The genetics and biology of calcium channels have been the subject of considerable investigation owing to their importance in fundamental neuronal processes and human diseases. L-type voltage-gated calcium channels are involved in learning, memory, and synaptic plasticity, and CACNA1C knock-out mice show notable deficits in long term potentiation. 34-37 Calcium “channelopathies” include mutations in CACNA1C and CACNB2 that cause Brugada syndrome types 3 and 4 (OMIM #611875 and #611876). 38In addition, Timothy syndrome (OMIM #601005), caused by mutations in CACNA1C, is a multisystem disorder including cognitive impairment and autism spectrum disorder. 39 Although Mendelian disorders are usually characterized by persistent pathological features, Mendelian calcium channelopathies can have episodic phenomena perhaps reminiscent of the episodic nature of psychotic disorders – for example, intermittent hypoglycemia and hypocalcemia in Timothy syndrome (CACNA1C), episodic ataxia (CACNA1A, CACNB4), migraine (CACNA1A), epilepsy (CACNA1H, CACNB4), periodic paralysis (CACNA1S), and malignant hyperthermia (CACNA1S, CACNA2D1). 31,39
