Molecular basis of inherited calcium channelopathies:role of mutations in pore-forming subunits

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:guanxinyang
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The pore-forming alpha subunits of voltage-gated calcium channels contain theessential biophysical machinery that underlies calcium influx in response to celldepolarization.In combination with requisite auxiliary subunits,these pore sub-units form calcium channel complexes that are pivotal to the physiology andpharmacology of diverse cells ranging from sperm to neurons.Not surprisingly,mutations in the pore subunits generate diverse pathologies,termedchannelopathies,that range from failures in excitation-contraction coupling tonight blindness.Over the last decade,major insights into the mechanisms ofpathogenesis have been derived from animals showing spontaneous or inducedmutations.In parallel,there has been considerable growth in our understandingof the workings of voltage-gated ion channels from a structure-function,regula-tion and cell biology perspective.Here we document our current understandingof the mutations underlying channelopathies involving the voltage-gated calciumchannel alpha subunits in humans and other species. The pore-forming alpha subunits of voltage-gated calcium channels contain theesse biophysical machinery that underlies calcium influx in response to cell depolarization. In combination with requisite auxiliary subunits, these pore sub-units form calcium channel complexes that are pivotal to the physiology and pharmacology of diverse cells ranging from sperm to neurons. Not surprisingly, mutations in the pore subunits generate diverse pathologies, termedchannelopathies, that range from failures in excitation-contraction coupling tonight blindness. Over the last decade, major insights into the mechanisms ofpathogenesis have been derived from animals showing spontaneous or inducedmutations. In parallel, there has been growth growth in our understanding of the workings of voltage-gated ion channels from a structure-function, regula- tion and cell biology perspective. Here we document our current understanding of the mutagenic underlying channel pathologies involving the voltage -gated calciumchannel alpha subunits in humans and other species.
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