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Diabetologia
Published in: Diabetologia 9/2014

01-09-2014 | Review

ATP-regulated potassium channels and voltage-gated calcium channels in pancreatic alpha and beta cells: similar functions but reciprocal effects on secretion

Authors: Patrik Rorsman, Reshma Ramracheya, Nils J. G. Rorsman, Quan Zhang

Published in: Diabetologia | Issue 9/2014

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Abstract

Closure of ATP-regulated K+ channels (KATP channels) plays a central role in glucose-stimulated insulin secretion in beta cells. KATP channels are also highly expressed in glucagon-producing alpha cells, where their function remains unresolved. Under hypoglycaemic conditions, KATP channels are open in alpha cells but their activity is low and only ~1% of that in beta cells. Like beta cells, alpha cells respond to hyperglycaemia with KATP channel closure, membrane depolarisation and stimulation of action potential firing. Yet, hyperglycaemia reciprocally regulates glucagon (inhibition) and insulin secretion (stimulation). Here we discuss how this conundrum can be resolved and how reduced KATP channel activity, via membrane depolarisation, paradoxically reduces alpha cell Ca2+ entry and glucagon exocytosis. Finally, we consider whether the glucagon secretory defects associated with diabetes can be attributed to impaired KATP channel regulation and discuss the potential for remedial pharmacological intervention using sulfonylureas.
Footnotes
1
The non-L-type Ca2+ current component in mouse alpha cells was previously attributed to activation of ω-conotoxin-sensitive N-type Ca2+ channels. However, it was subsequently discovered that such channels are expressed at very low levels in alpha cells, whereas ω-agatoxin-sensitive P/Q-type Ca2+ channels are highly expressed. Pharmacological experiments revealed that ω-conotoxin had no effect on alpha cells Ca2+ currents in the presence of ω-agatoxin. We therefore conclude that ω-conotoxin unspecifically blocks P/Q-type Ca2+ channels in alpha cells. Here, non-L-type Ca2+ channels are therefore referred to as P/Q-type Ca2+ channels even when referred to as N-type in the original publications.
 
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Metadata
Title
ATP-regulated potassium channels and voltage-gated calcium channels in pancreatic alpha and beta cells: similar functions but reciprocal effects on secretion
Authors
Patrik Rorsman
Reshma Ramracheya
Nils J. G. Rorsman
Quan Zhang
Publication date
01-09-2014
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 9/2014
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-014-3279-8

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