Cx36-mediated coupling reduces beta-cell heterogeneity, confines the stimulating glucose concentration range, and affects insulin release kinetics.
We studied the effect of gap junctional coupling on the excitability of beta-cells in slices of pancreas, which provide a normal environment for islet cells. The electrophysiological properties of beta-cells from mice (C57Bl/6 background) lacking the gap junction protein connexin36 (Cx36(-/-)) were compared with heterozygous (Cx36(+/-)) and wild-type littermates (Cx36(+/+)) and with frequently used wild-type NMRI mice. Most electrophysiological characteristics of beta-cells were found to be unchanged after the knockout of Cx36, except the density of Ca(2+) channels, which was increased in uncoupled cells. With closed ATP-sensitive K(+) (K(ATP)) channels, the electrically coupled beta-cells of Cx36(+/+) and Cx36(+/-) mice were hyperpolarized by the membrane potential of adjacent, inactive cells. Additionally, the hyperpolarization of one beta-cell could attenuate or even stop the electrical activity of nearby coupled cells. In contrast, beta-cells of Cx36(-/-) littermates with blocked K(ATP) channels rapidly depolarized and exhibited a continuous electrical activity. Absence of electrical coupling modified the electrophysiological properties of beta-cells consistent with the reported increase in basal insulin release and altered the switch on/off response of beta-cells during an acute drop of the glucose concentration. Our data indicate an important role for Cx36-gap junctions in modulating stimulation threshold and kinetics of insulin release.
Speier
Stephan
S
The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden. stephan.speier@ki.se
Gjinovci
Asllan
A
Charollais
Anne
A
Meda
Paolo
P
Rupnik
Marjan
M
D000818:Animals; D017630:Connexins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004594:Electrophysiology; D005947:Glucose / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D000097004:Gap Junction delta-2 Protein
D017630:Connexins; D005947:Glucose; D007328:Insulin; D000097004:Gap Junction delta-2 Protein