title: T-type calcium channels: functional regulation and implication in pain signaling.
abstract: Low-voltage-activated T-type Ca(2+) 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 Cav3.2 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.
authors.affiliation: Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sekiguchi
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
mesh_terms: D000700:Analgesics; D001205:Ascorbic Acid / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000378:metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology; D058990:Molecular Targeted Therapy; D009475:Neurons, Afferent / Q000378:metabolism; D010148:Intractable Pain / Q000235:genetics* / Q000503:physiopathology; D020033:Protein Isoforms; D011494:Protein Kinases / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D013373:Substance P / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000700:Analgesics; D020747:Calcium Channels, T-Type; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D013373:Substance P; D018698:Glutamic Acid; D011494:Protein Kinases; D001205:Ascorbic Acid; D006862:Hydrogen Sulfide