Glucose and a-ketoisocaproate induce transient inward currents in rat pancreatic beta cells

Best, Leonard

doi:10.1007/s001250050635

Cited by 51 publications

(50 citation statements)

References 23 publications

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“…Firstly, potentiation of the current by tolbutamide was highly dependent on the presence of glucose. As reported previously [9,10,11] and confirmed in the present study, the sulphonylureas had little or no effect on VRAC activity of in the absence of the sugar. Secondly, tolbutamide was observed to have no effect on VRAC activity in conventional wholecell recordings where glucose metabolism was abolished [18], and the drug did not influence channel activity in perforated membrane vesicles or excised patches.…”

Section: Discussionsupporting

confidence: 91%

“…The pipette solution was similar to that described above except that K + was replaced by Cs + in order to eliminate K + currents. The inward current recorded under similar conditions has previously been described [9,10], and is thought to represent the VRAC activity. In order to quantify changes in VRAC activity, mean current amplitudes were measured from 60-second segments of recording under various conditions using pClamp6 software (Axon Instruments, Foster City, Calif., USA) [10].…”

Section: Methodsmentioning

confidence: 65%

“…Whole-cell recordings were made from cells voltage-clamped at −65 mV using the perforated patch recording technique. Under such conditions, VRAC activation generates a noisy inward current with occasional discrete channel events [9,10].…”

Section: Effects Of Tolbutamide On Beta Cell Electrical Activitymentioning

confidence: 99%

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Tolbutamide potentiates the volume-regulated anion channel current in rat pancreatic beta cells

2004

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Aims/hypothesis. Hypoglycaemic sulphonylureas are thought to stimulate insulin release by binding to a sulphonylurea receptor, closing K ATP channels and inducing electrical activity. However, the fact that these drugs stimulate insulin release at high glucose concentrations where K ATP channels are closed suggests additional ionic actions. The aim of this study was to test the hypothesis that sulphonylureas influence the current of the glucose-and volume-regulated anion channel. Methods. Electrical and ion-channel activity were recorded in isolated rat beta cells using the patchclamp technique. 86 Rb + efflux was measured using intact islets. Beta cell volume was measured using a video-imaging technique. Results. In the absence of glucose, tolbutamide (100 µmol/l) transiently depolarised the cells. In the presence of glucose (5 mmol/l), tolbutamide evoked a sustained period of electrical activity, whilst at 10 mmol/l glucose, the drug evoked a pronounced 'silent' depolarisation. In the absence of glucose, tolbutamide inhibited 86 Rb + efflux. However, at 10 mmol/l glucose, tolbutamide induced a transient stimulation of efflux. Tolbutamide potentiated the whole-cell volume-regulated anion conductance in a glucose-dependent manner with an EC 50 of 85 µmol/l. In single channel recordings, tolbutamide increased the channel-open probability. Tolbutamide caused beta cell swelling in the presence of glucose, but not in its absence. Conclusions/interpretation. Tolbutamide can induce beta cell electrical activity by potentiating the glucose-and volume-regulated anion channel current. This effect is probably not due to a direct effect of the drug on the channel, but could be secondary to a metabolic action in the beta cell.

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Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 65%

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Tolbutamide potentiates the volume-regulated anion channel current in rat pancreatic beta cells

2004

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“…Glucose and Ca 2+ , which activate volume-sensitive or Ca 2+ -dependent anion channels, significantly stimulated the uptake of selenite (Ulrich and Shrift, 1968;Arvy, 1989;Best, 1997Best, , 1999Yu and Wu, 1999), and selenite may enter maize roots through anion channels. NPPB, 9-CA, NPAA, TEACl, NA, and DIDS are different types of anion-channels inhibitors.…”

Section: Discussionmentioning

confidence: 97%

Physiological characteristics of selenite uptake by maize roots in response to different pH levels

Zhang

Shi

et al. 2010

Z. Pflanzenernähr. Bodenk.

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In selenite solutions, H 2 SeO 3 , HSeO À 3 , and SeO 2À 3 are in equilibrium in proportions that vary with solution pH. The physiological characteristics of selenite uptake were studied with excised roots of maize (Zea mays L.) seedlings at pH 3.0, 5.0, and 8.0. The results showed that 0.10 mM 2,4-dinitrophenol (DNP), 1.0 mM sodium fluoride (NaF), and a temperature of 4°C inhibited selenite uptake by maize roots by 16%, 20%, and 23% at pH 3.0, by up to 80%, 79%, and 78% at pH 5.0, and by 5%, 9%, and 16% at pH 8.0. Hence, selenite may enter roots at pH 5.0 in an energy-dependent manner, in contrast to pH 3.0 and 8.0. The uptake kinetics for selenite were determined for excised roots of maize, and the curves were linear at pH 3.0 and 8.0, but saturated at pH 5.0, showing that carrier-mediated uptake of selenite occurred at pH 5.0, but not at pH 3.0 or 8.0. Further studies showed that HgCl 2 and AgNO 3 inhibited selenite uptake separately by 81% and 76% at pH 3.0 and indicated that selenite was absorbed by maize roots through aquaporins at pH 3.0. At pH 8.0, anion-channel inhibitors only inhibited a small fraction of selenite uptake, indicating that the major absorption pathway of SeO 2À 3 species into roots was not absorbed passively through anion channels, but might involve other processes. According to these results, it is proposed that selenite uptake occurs via different mechanisms depending on its species in solution in response to pH levels.

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“…This could also explain why inhibitors of this cotransporter inhibit insulin release Sandstrom, 1990 (Best, 1997; Fig. I B).…”

Section: Monocarboxylate Transportmentioning

confidence: 92%

Anion fluxes, volume regulation and electrical activity in the mammalian pancreatic beta‐cell

Best

Brown²,

Tomlinson³

1997

Experimental Physiology

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Glucose and a-ketoisocaproate induce transient inward currents in rat pancreatic beta cells

Cited by 51 publications

References 23 publications

Tolbutamide potentiates the volume-regulated anion channel current in rat pancreatic beta cells

Tolbutamide potentiates the volume-regulated anion channel current in rat pancreatic beta cells

Physiological characteristics of selenite uptake by maize roots in response to different pH levels

Anion fluxes, volume regulation and electrical activity in the mammalian pancreatic beta‐cell

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