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.
Sher
E
E
Eli Lilly and Co., Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey GU20 6PH, United Kingdom. sher_emanuele@lilly.com
Giovannini
F
F
Codignola
A
A
Passafaro
M
M
Giorgi-Rossi
P
P
Volsen
S
S
Craig
P
P
Davalli
A
A
Carrera
P
P
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