[P/Q-type voltage-dependent calcium channels in neurological disease].
BACKGROUND
Voltage-dependent calcium channels (VDCC) are hetero-multimeric complexes that mediate calcium influx into cells in response to changes in membrane potential. The alpha1A subunit, encoded by the CACNA1A gene, is the pore-forming structure specific to the neuronal P/Q-type voltage-dependent calcium channels (P/QCC), present exclusively in neurons. The ancillary subunits beta, alpha2delta and gamma, which are common to other VDCC, modulate alpha1A activity. P/QCC are involved in neuronal plasticity and survival, and mediate fast neurotransmission in the central and peripheral nervous system. Their highest levels of expression are found in the Purkinje cell layer of the cerebellum and in the hippocampus.


METHODS
Congenital and acquired disturbances of the P/QCCs lay behind some neurological diseases, such as spinocerebellar ataxia type 6, episodic ataxia type 2 and paraneoplastic cerebellar degeneration; familial hemiplegic migraine; generalized convulsive epilepsy, generalized absence epilepsy and myasthenic syndrome of Lambert-Eaton.


CONCLUSIONS
In this article, the structure and modulation of normal P/QCCs, and the neurological diseases caused by disturbances in these are reviewed. Electrophysiological characterization of mutated P/QCCs has yielded decreased calcium conductance in every case, compared with wild type channels. Research about calcium channelopathies should clarify how altered channel function produces disease and lead to new treatments for these conditions.
Gazulla
J
J
Servicio de Neurología, Hospital Universitario Miguel Servet, Zaragoza. josegazulla@wanadoo.es
Tintore
M
M
D000818:Animals; D001259:Ataxia / Q000235:genetics; D020274:Autoimmune Diseases of the Nervous System / Q000209:etiology / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology; D020864:Calcium Channels, N-Type / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D020865:Calcium Channels, P-Type / Q000235:genetics / Q000502:physiology; D020907:Calcium Channels, Q-Type / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants; D008881:Migraine Disorders / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D009422:Nervous System Diseases / Q000235:genetics / Q000503:physiopathology*; D020361:Paraneoplastic Syndromes, Nervous System / Q000209:etiology / Q000276:immunology; D021122:Protein Subunits; D051381:Rats; D013329:Structure-Activity Relationship
D002118:Calcium; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; C105656:CACNA1A protein, human