Activation of an anion conductance and beta‐cell depolarization during hypotonically induced insulin release

Best, Leonard; Miley, HE; Ap, Yates

doi:10.1113/expphysiol.1996.sp003993

Cited by 75 publications

(97 citation statements)

References 9 publications

(28 reference statements)

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“…The increase in cell volume observed following the addition of n-octanol under isotonic conditions has not previously been recorded with other VRAC inhibitors. We suggest that this phenomenon reflects the high effectiveness of n-octanol as a VRAC inhibitor, and is consistent with the suggestion that the conductance in b-cells is active even under isosmotic conditions [7].…”

Section: Octanoic (Caprylic ) Acidsupporting

confidence: 72%

Effects of octane derivatives on activity of the volume-regulated anion channel in rat pancreatic β-cells

Best

Brown

2013

Pharmacological Reports

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Abstract:Background: Saturated free fatty acids (FFAs) have a dual action on pancreatic b-cells, consisting of an initial enhancement and subsequent suppression of glucose-induced electrical activity and insulin release. These stimulatory and inhibitory effects have been attributed, at least in part, to the activation and inhibition, respectively, of the volume-regulated anion channel (VRAC) by FFAs. Both effects were independent of their metabolism. We have now investigated the effects of related aliphatic compounds in order to further define the determinants of FFA interaction with VRAC. Methods: b-Cell VRAC and electrical activity were measured by conventional whole-cell and perforated patch recording, respectively. Cell volume was measured using a video-imaging technique. Results: In common with octanoic acid, addition of methyl octanoate or n-octanol resulted in a rapid, pronounced and reversible inhibition of VRAC activity. Addition of n-octane had no significant effect on VRAC activity. n-Octanol had a biphasic effect on b-cell membrane potential, namely a small transient depolarization followed by a marked hyperpolarization. n-Octanol was also found to prevent regulatory volume decrease in cells exposed to a hypotonic medium, consistent with VRAC inhibition. Conclusion: It is suggested that methyl octanoate and n-octanol can mimic the effects of FFAs on the pancreatic b-cell via modulation of VRAC activity. The structural requirements for this effect appear to be a medium or long chain aliphatic compound containing at least one oxygen atom.

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Section: Octanoic (Caprylic ) Acidsupporting

confidence: 72%

Effects of octane derivatives on activity of the volume-regulated anion channel in rat pancreatic β-cells

Best

Brown

2013

Pharmacological Reports

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“…1). The pattern of this inward current closely resembled that previously shown to accompany hypotonically induced cell swelling (Best et al 1996). In accordance with this, methylglyoxal activated an outwardly rectifying conductance in voltage-pulse experiments using Cs + -rich solutions.…”

supporting

confidence: 65%

“…In accordance with this, methylglyoxal activated an outwardly rectifying conductance in voltage-pulse experiments using Cs + -rich solutions. This conductance was virtually identical to the volume-sensitive anion conductance activated by exposure to hypotonic solutions (Best et al 1996). The application of 1 mmol 1-1 methylglyoxal to single rat ,8 -cells resulted in an increase in cell volume to a relative value of 1' 33 ± 0'03 (mean ± S.E.M., n = 4) after 10 min of exposure.…”

mentioning

confidence: 54%

General – Ion Channels

1998

The Journal of Physiology

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Arterioles provide a major component of cerebrovascular resistance and regulate blood flow into the capillary bed. Electrical activity has a pivotal role in the control of arteriolar calibre and so we are investigating the basis of resting potential. There are recent suggestions that novel 'background' K+ channel are involved (e.g. Duprat et al. 1997;Quinn & Beech, 1997). Direct patch-clamp recordings were made from smooth muscle cells embedded in isolated but intact cerebral arterioles of 20-40 f.lm diameter. 36PAmphotericin B was used to perforate the cell-attached patch in current-clamp recordings and the patch pipette solution included 130 mM KCI. External diameter measurements were made from arterioles using a videodimension analyser. Recordings were at 22-25 QC and the standard extracellular solution contained (mM): 130 NaCl, 5 KCl, 1'5 CaCI 2 , 1'2 MgCI2' 8 glucose and 10 Hepes (pH 7'4).Arterioles constricted in response to K+: for example, > 95 % of arterioles constricted in response to 60 mM K+ and the mean constriction as a percentage of basal arteriolar diameter was 33'7 ± 2'9 % (n = 36, mean ± S.E.M.). In current clamp, raising the K+ concentration from 5 mM depolarized arterioles by 13'8 ± 2'5 mV for 10 mM K+, 28'0 ± 3'6 mV for 20 mM K+, 46'8 ± 2'6 mV for 40 mM K+, and 62'8 ± 2'0 mV for 60 mM K+ (n = 4 for each). The mean resting potential in 5 mM K+ was -76'4 ± 5' 1 mV (n = 7).To investigate which K+ channel types were involved, we applied a combination of K+ channel blockers to inhibit inward rectifier, BK ca , K ATP ' aminopyridine-sensitive K v , and apamin-sensitive channels: 0'1 mM Ba 2 +, 4 mM tetraethylammonium, 100 nM penitrem A, 1 jlM glibenclamide, 1 mM 3,4-diaminopyridine and 100 nM apamin. The cocktail induced sustained or oscillating constrictions in fourteen out of thirty-eight arterioles, but in the remaining twenty-four arterioles there was no effect , even though there was constriction in response to 60 mM K+. In current-clamp, the cocktail induced a sustained depolarization in one arteriole, a transient but not sustained depolarization in one arteriole, and had no effect in three arterioles. For all of t he blockers, except apamin, we have shown in separate experiments that each agent was effective against the relevant K+ channel. The data suggest the presence of a K+ channel type that plays a major role in determining resting potential and that is not an inward rectifier, a BKca channel or an aminopyridine-sensitive Kv channel. and cytoplasmic modulatory /3 subunits. Regulation of different types of K+ channels by protein phosphorylation and oxygen has been described for several tissues and cell types. To elucidate whether 02-sensing is an intrinsic property of the channel proteins themselves, we have studied the modulation by hypoxia of cloned voltagedependent K+ channels, and the possible role of the accessory /3 subunits, in transfected mammalian cells. The cDNA encoding two of these voltage-dependent K+ channels , Shake?' and K v4.2, which give rise to rapidly activating and ...

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“…5B). In a previous study, 100 mol/l DIDS was found to block 67% of hypotonically induced insulin release from rat islets (38). In contrast, hypotonically induced secretion was unaffected by 100 mol/l niflumic acid, even though niflumic acid was found to be a more effective blocker of I Cl,islet (P Ͻ 0.05) (compare Fig.…”

Section: Resultsmentioning

confidence: 89%

“…3A), followed by a spontaneous regulatory volume decrease (RVD). RVDs have been observed previously after the application of hypotonic solutions to rat ␤-cells (36,37), RINm5F cells (38), and mouse ␤-cells (39). When the hypotonic solution also contained 100 mol/l niflumic acid, the RVD was largely blocked, and cell volume increased significantly by an additional 29.5% over that observed when hypotonic solution alone was applied (P Ͻ 0.05) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Chloride Channels Regulate HIT Cell Volume but Cannot Fully Account for Swelling-Induced Insulin Secretion

Kinard¹,

Goforth²,

Qing³

et al. 2001

Diabetes

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Insulin-secreting pancreatic islet ␤-cells possess anionpermeable Cl؊ channels (I Cl,islet ) that are swelling-activated, but the role of these channels in the cells is unclear. The Cl ؊ channel blockers 4,4-diisothiocyanostilbene-2,2-disulfonic acid (DIDS) and niflumic acid were evaluated for their ability to inhibit I Cl,islet in clonal ␤-cells (HIT cells). Both drugs blocked the channel, but the blockade due to niflumic acid was less voltage-dependent than the blockade due to DIDS. HIT cell volume initially increased in hypotonic solution and was followed by a regulatory volume decrease (RVD). The addition of niflumic acid and, to a lesser extent, DIDS to the hypotonic solution potentiated swelling and blocked the RVD. In isotonic solution, niflumic acid produced swelling, suggesting that islet Cl ؊ channels are activated under basal conditions. The channel blockers glyburide, gadolinium, or tetraethylammonium-Cl did not alter hypotonic-induced swelling or volume regulation. The Na/K/2Cl transport blocker furosemide produced cell shrinkage in isotonic solution and blocked cell swelling normally induced by hypotonic solution. Perifused HIT cells secreted insulin when challenged with hypotonic solutions. However, this could not be completely attributed to I Cl,islet -mediated depolarization, because secretion persisted even when Cl ؊ channels were fully blocked. To test whether blocker-resistant secretion occurred via a distal pathway, distal secretion was isolated using 50 mmol/l potassium and diazoxide. Under these conditions, glucose-dependent secretion was blunted, but hypotonically induced secretion persisted, even with Cl ؊ channel blockers present. These results suggest that ␤-cell swelling stimulates insulin secretion primarily via a distal I Cl,isletindependent mechanism, as has been proposed for K ATPindependent glucose-and sulfonylurea-stimulated insulin secretion. Reverse transcriptase-polymerase chain reaction of HIT cell mRNA identified a CLC-3 transcript in HIT cells. In other systems, CLC-3 is believed to mediate swelling-induced outwardly rectify-

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Activation of an anion conductance and beta‐cell depolarization during hypotonically induced insulin release

Cited by 75 publications

References 9 publications

Effects of octane derivatives on activity of the volume-regulated anion channel in rat pancreatic β-cells

Effects of octane derivatives on activity of the volume-regulated anion channel in rat pancreatic β-cells

General – Ion Channels

Chloride Channels Regulate HIT Cell Volume but Cannot Fully Account for Swelling-Induced Insulin Secretion

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