Oscillation of gap junction electrical coupling in the mouse pancreatic islets of Langerhans.

Andreu, Etelvina; Soria, Bernat; Sánchez-Andrés, Juan Vicente

doi:10.1113/jphysiol.1997.sp021899

Cited by 60 publications

(61 citation statements)

References 27 publications

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“…To understand how loss of Cx36 leads to these changes, it is necessary to identify the signals that are transferred by Cx36 channels, and to evaluate the extent of such a transfer in the environment of intact pancreatic islets. Previous electrophysiological studies have shown that ionic coupling extends to large regions of the islets, as judged by both the electrical synchronisation of beta cells and the intercellular diffusion of electrotonic currents [5,7,10,22]. In contrast, experiments testing the cell exchange of radioactive precursors [11] and exogenous tracers [8,12,18] have suggested that metabolic coupling within pancreatic islets may be restricted to territories comprising only a few beta cells [8,11,15].…”

mentioning

confidence: 89%

“…In pancreatic islets, beta cells are linked by Cx36 channels [14,20,24,25], which account for electrical coupling [5,7,10,13,15,22,23], as well as for the intercellular synchronisation of glucose-induced electrical activity [5,10,15,22] and Ca 2+ transients [15,21,23,35]. The same channels also allow beta cells to exchange cytosolic molecules [11,15,23] and exogenous tracers [8, 12, 17-19, 21, 29].…”

Section: Discussionmentioning

confidence: 99%

“…current-carrying ions and other small cytosolic molecules [7][8][9][10][11][12][13][14][15]. Recent evidence has shown that these exchanges ensure the synchronisation and recruitment of beta cells during insulin secretion [9,10,[15][16][17][18][19][20][21][22][23].…”

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confidence: 99%

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Beta cells preferentially exchange cationic molecules via connexin 36 gap junction channels

2007

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Aims/hypothesis Pancreatic beta cells are connected by gap junction channels made of connexin 36 (Cx36), which permit intercellular exchanges of current-carrying ions (ionic coupling) and other molecules (metabolic coupling). Previous studies have suggested that ionic coupling may extend to larger regions of pancreatic islets than metabolic coupling. The aim of the present study was to investigate whether this apparent discrepancy reflects a difference in the sensitivity of the techniques used to evaluate beta cell communication or a specific characteristic of the Cx36 channels themselves. Methods We microinjected several gap junction tracers, differing in size and charge, into individual insulin-producing cells and evaluated their intercellular exchange either within intact islets of control, knockout and transgenic mice featuring beta cells with various levels of Cx36, or in cultures of wildtype and Cx36-transfected MIN6 cells. Results We found that (1) Cx36 channels favour the exchange of cations and larger positively charged molecules between beta cells at the expense of anionic molecules; (2) this exchange occurs across sizable portions of pancreatic islets; and (3) during glibenclamide (known as glyburide in the USA and Canada) stimulation beta cell coupling increases to an extent that varies for different gap junction-permeant molecules. Conclusions/interpretationThe data show that beta cells are extensively coupled within pancreatic islets via exchanges of mostly positively charged molecules across Cx36 channels. These exchanges selectively increase during stimulation of insulin secretion. The identification of this permselectivity is expected to facilitate the identification of endogenous permeant molecules and of the mechanism whereby Cx36 signalling significantly contributes to the modulation of insulin secretion.

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confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Beta cells preferentially exchange cationic molecules via connexin 36 gap junction channels

2007

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“…We and others have previously reported that the gap junctional conductance only changes marginally (approx. 10%, if at all) during the active and silent phases (Mears et al 1995;Göpel et al 1999b; but see Andreu et al 1997). Assuming that the membrane potential in the neighbouring cells oscillates in the same way as it does in the cell in direct contact with the patch electrode, the gap junctional conductance (G j,tot ) can be calculated using the relationship (Mears et al 1995) …”

Section: (A ) Evidence For Electrical Coupling Between B-cells In Intmentioning

confidence: 99%

Cell coupling in mouse pancreatic β-cells measured in intact islets of Langerhans

Zhang

Galvanovskis

Abdulkader

et al. 2008

Phil. Trans. R. Soc. A.

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The perforated whole-cell configuration of the patch-clamp technique was applied to functionally identified b-cells in intact mouse pancreatic islets to study the extent of cell coupling between adjacent b-cells. Using a combination of current-and voltage-clamp recordings, the total gap junctional conductance between b-cells in an islet was estimated to be 1.22 nS. The analysis of the current waveforms in a voltage-clamped cell (due to the firing of an action potential in a neighbouring cell) suggested that the gap junctional conductance between a pair of b-cells was 0.17 nS. Subthreshold voltage-clamp depolarization (to K55 mV) gave rise to a slow capacitive current indicative of coupling between b-cells, but not in non-b-cells, with a time constant of 13.5 ms and a total charge movement of 0.2 pC. Our data suggest that a superficial b-cell in an islet is in electrical contact with six to seven other b-cells. No evidence for dye coupling was obtained when cells were dialysed with Lucifer yellow even when electrical coupling was apparent. The correction of the measured resting conductance for the contribution of the gap junctional conductance indicated that the whole-cell K ATP channel conductance (G K,ATP ) falls from approximately 2.5 nS in the absence of glucose to 0.1 nS at 15 mM glucose with an estimated IC 50 of approximately 4 mM. Theoretical considerations indicate that the coupling between b-cells within the islet is sufficient to allow propagation of [Ca 2C ] i waves to spread with a speed of approximately 80 mm s K1 , similar to that observed experimentally in confocal [Ca 2C ] i imaging.

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“…The challenge is to understand the origin of these oscillations. Various detailed biophysical models of oscillations in networks of pancreatic β cells have been proposed, in which the importance of the heterogeneity of individual cells [9] and the emergence of oscillatory behavior upon coupling nonoscillatory cells [10,11] have been highlighted. Here I take a different approach in which I bring together these two ideas while simplifying the physics as far as possible to produce a minimal qualitative model for the phenomenon.…”

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confidence: 99%

Emergent global oscillations in heterogeneous excitable media: The example of pancreaticβcells

Cartwright¹

2000

Phys. Rev. E

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Using the standard van der Pol-FitzHugh-Nagumo excitable medium model I demonstrate a novel generic mechanism, diversity, that provokes the emergence of global oscillations from individually quiescent elements in heterogeneous excitable media. This mechanism may be operating in the mammalian pancreas, where excitable β cells, quiescent when isolated, are found to oscillate when coupled despite the absence of a pacemaker region.

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Oscillation of gap junction electrical coupling in the mouse pancreatic islets of Langerhans.

Cited by 60 publications

References 27 publications

Beta cells preferentially exchange cationic molecules via connexin 36 gap junction channels

Beta cells preferentially exchange cationic molecules via connexin 36 gap junction channels

Cell coupling in mouse pancreatic β-cells measured in intact islets of Langerhans

Emergent global oscillations in heterogeneous excitable media: The example of pancreaticβcells

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