Voltage-operated calcium channel heterogeneity in pancreatic beta cells: physiopathological implications.
Voltage-operated calcium channels play crucial roles in stimulus-secretion coupling in pancreatic beta cells. A growing body of evidence indicates that these channels in beta cells are heterogeneous. In particular, not all the high-threshold calcium channels expressed belong to the best known L-type. In rat insulinoma cells, for example, L, N, and P/Q-type channels are present, while in human beta cells L-type and P/Q-type dominate. Where present, N-type and P/Q-type channels participate, alongside with the dominant L-type, in the control of sugar- or depolarization-induced hormone release. Distinct biophysical properties and selective modulation of the channel subtypes are likely to play important physiological roles. T-type channels are involved in beta cell apoptosis, while calcium channel autoantibodies recognizing high-threshold channels in beta cells, have been described both in neurological and diabetic patients. Subtype-selective calcium channel drugs have the potential for being beneficial in beta cell pathological states.
Eli Lilly and Co., Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey GU20 6PH, United Kingdom. sher_emanuele@lilly.com
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Sher
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Giovannini
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Codignola
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Passafaro
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Giorgi-Rossi
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Volsen
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Craig
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Davalli
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Carrera
D000818:Animals; D015220:Calcium Channels / Q000737:chemistry / Q000145:classification* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008564:Membrane Potentials; D009468:Neuromuscular Diseases / Q000378:metabolism*; D014018:Tissue Distribution
D015220:Calcium Channels; D007328:Insulin; D005947:Glucose