T-type calcium channels: Functional regulation and implication in pain signaling

Low-voltage-activated t-type ca2+ channels (t-channels),especially cav3.2 among the three isoforms (cav3.1,cav3.2,and cav3.3),are now considered to play pivotal roles in processing of pain signals. cav3.2 t-channels are functionally modulated by extracellular substances such as hydrogen sulfide and ascorbic acid,by intracellular signaling molecules including protein kinases,and by glycosylation. cav3.2 t-channels are abundantly expressed in both peripheral and central endings of the primary afferent neurons,regulating neuronal excitability and release of excitatory neurotransmitters such as substance?p and glutamate,respectively. functional upregulation of ca v3.2 t-channels is involved in the pathophysiology of inflammatory,neuropathic,and visceral pain. thus,cav3.2 t-channels are considered to serve as novel targets for development of drugs for treatment of intractable pain resistant to currently available analgesics. © the japanese pharmacological society.