High-conductance K+ channel in pancreatic islet cells can be activated and inactivated by internal calcium

Findlay, Ian; Dunne, Mark J.; Petersen, O. H.

doi:10.1007/bf01868748

Cited by 145 publications

(81 citation statements)

References 29 publications

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“…All experiments were carried out at 37°C. For electrophysiology and microfluorimetry studies of isolated fl-cells, tissue was prepared as previously described (Findlay et al, 1985). Single KATP Brifish Joumal of Phamacology (1996) 119, 911 916 channel currents were recorded by use of patch-clamp techniques (Hamill et al, 1981) (Lebrun et al, 1996).…”

Section: Methodsmentioning

confidence: 99%

Elevation of cytosolic calcium by imidazolines in mouse islets of Langerhans: implications for stimulus‐response coupling of insulin release

Shepherd

Hashmi

Kane

et al. 1996

British J Pharmacology

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[Ca2+], under any experimental condition tested. 5 The putative endogenous ligand of imidazoline receptors, agmatine (1 gM -1 mM), blocked KATP channels in isolated patches of f-cell membrane, but effects upon [Ca2+], could not be further investigated since agmatine disrupts fura-2 fluorescence. 6 In conclusion, the present study shows that imidazolines will evoke rises in [Ca2+] in intact islets, and this provides an explanation to account for the previously described effects of imidazolines on KATP channels, the cell membrane potential and insulin secretion in pancreatic f-cells.

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Section: Methodsmentioning

confidence: 99%

Elevation of cytosolic calcium by imidazolines in mouse islets of Langerhans: implications for stimulus‐response coupling of insulin release

Shepherd

Hashmi

Kane

et al. 1996

British J Pharmacology

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“…TEA blocks numerous Kv channels other than Kv2.1 that may be expressed in insulin-secreting cells (5,11,16,17,(32)(33)(34). Additionally, TEA blocks K Ca currents, which are present in insulin-secreting cells (33,34,(43)(44)(45)(46)(47)(48) and can partially block K ATP channels (34,49). The ability of C-1 and ITX together to replicate the oscillatory effects of TEA in a portion of cells strongly suggests that the response to TEA results in part from blockade of both Kv2.1 and BK Ca channels.…”

Section: Fig 3 C-1 Inhibits Kv21 Currents In Min6 Cellsmentioning

confidence: 99%

Inhibition of Kv2.1 Voltage-dependent K+Channels in Pancreatic β-Cells Enhances Glucose-dependent Insulin Secretion

MacDonald¹,

Sewing²,

Wang³

et al. 2002

Journal of Biological Chemistry

162

169

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Voltage-dependent (Kv) outward K ؉ currents repolarize ␤-cell action potentials during a glucose stimulus to limit Ca 2؉ entry and insulin secretion. Dominant-negative "knockout" of Kv2 family channels enhances glucose-stimulated insulin secretion. Here we show that a putative Kv2.1 antagonist (C-1) stimulates insulin secretion from MIN6 insulinoma cells in a glucose-and dosedependent manner while blocking voltage-dependent outward K ؉ currents. C-1-blocked recombinant Kv2.1-mediated currents more specifically than currents mediated by Kv1, -3, and -4 family channels (Kv1.4, 3.1, 4.2). Additionally, C-1 had little effect on currents recorded from MIN6 cells expressing a dominant-negative Kv2.1 ␣-subunit. The insulinotropic effect of acute Kv2.1 inhibition resulted from enhanced membrane depolarization and augmented intracellular Ca 2؉ responses to glucose. Immunohistochemical staining of mouse pancreas sections showed that expression of Kv2.1 correlated highly with insulin-containing ␤-cells, consistent with the ability of C-1 to block voltage-dependent outward K ؉ currents in isolated mouse ␤-cells. Antagonism of Kv2.1 in an ex vivo perfused mouse pancreas model enhanced first-and second-phase insulin secretion, whereas glucagon secretion was unaffected. The present study demonstrates that Kv2.1 is an important component of ␤-cell stimulus-secretion coupling, and a compound that enhances, but does not initiate, ␤-cell electrical activity by acting on Kv2

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“…The cell was held at -70 mV and hyperpolarizing and depolarizing pulses of 10 mV amplitude and 100 ms duration were applied alternately at a rate of 55 Hz. Most of the resulting current flows through ATP-sensitive K-channels since voltage-dependent currents are not activated by these low pulse amplitudes [22] and activation of Ca-dependent Kchannels [23] was prevented by buffering the free Ca 2+ in the intracellular solution to 0.06 I, tmol/1.…”

Section: Whole-cell Currentsmentioning

confidence: 99%

The ATP- and tolbutamide-sensitivity of the ATP-sensitive K-channel from human pancreatic B cells

et al. 1989

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Summary. The ATP-and sulphonylurea-sensitivity of the ATP-sensitive K-channel was measured in human pancreatic B cells. In inside-out patches, half-maximal inhibition of channel activity was produced by 10 p~mol/l ATP (with 2 mM Mg 2+) and ATP-inhibition was partially antagonised by ADP. A significantly lower sensitivity to ATP was found in whole-cell recordings. Tolbutamide inhibited whole-cell ATPsensitive K-currents half-maximally at 18 ~tmol/l; the sensitivity to tolbutamide ~vas somewhat less in the inside-out patch.Ca-activated K-channels were unaffected by tolbutamide (10 mmol/1). These results resemble those found for rodent B cells and suggest that sulphonylureas exert their therapeutic effects in Type 2 (non-insulin dependent) diabetes by inhibition of the ATP-sensitive K-channel.Key words: ATP-sensitive K-channel, pancreatic B cell, human islet, sulphonylurea, tolbutamide, insulin secretion.The activity of the ATP-sensitive K-channel is thought to play a central role in the physiological regulation of insulin secretion from the pancreatic B-cell [1,2]. Studies of rodent B cells and B cell lines have led to the proposal that an increase in the cytosolic ATP/ADP ratio, resulting from glucose metabolism, inhibits channel activity. This produces membrane depolarization and precipitates a chain of events that culminates in insulin secretion.The channel is also the target for the hypoglycaemic sulphonylureas used clinically in the treatment of Type 2 (non-insulin-dependent) diabetes mellitus. These drugs inhibit channel activity in rodent B cells [3][4][5][6][7] and thereby stimulate electrical activity and insulin release [8]. It has therefore been suggested that a defect in the regulation of the ATP-sensitive K-channel may be involved in the initial pathology of Type 2 diabetes [9].Information about the properties of this channel in man is scarce. We have shown previously that the normal human B-cell possesses a K-channel inhibited by both ATP and the sulphonylurea, tolbutamide [9]. A similar channel is also found in human insulinoma ceils [10]. In this paper we present a detailed analysis of the properties of the ATP-sensitive K-channel of the human B cell. Our results indicate that the rodent B cell constitutes a good model for that of the human and provide support for the idea that the therapeutic action of tolbutamide in man is mediated via inhibition of the ATP-sensitive K-channel. Materials and methods PreparationHuman pancreata were removed (with permission) from nondiabetic, heart-beating cadaw.~r organ donors and islets of Langerhans isolated under aseptic conditions using a method similar to that described previously [11]. "[here were 2 male donors aged 27 and 37, and 3 female donors aged 19, 55 and 58. In brief, the pancreatic duct was cannulated and the pancreas distended with 2 ml/g prewarmed collagenase (6 mg/ml) in Iq[ank's solution. The pancreas was incubated in a water bath at 39~ for 25 rain then cooled rapidly in ice cold Hank's containing 20 mmol/1 HEPES and 5 g/1 bovine serum albumin....

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High-conductance K+ channel in pancreatic islet cells can be activated and inactivated by internal calcium

Cited by 145 publications

References 29 publications

Elevation of cytosolic calcium by imidazolines in mouse islets of Langerhans: implications for stimulus‐response coupling of insulin release

Elevation of cytosolic calcium by imidazolines in mouse islets of Langerhans: implications for stimulus‐response coupling of insulin release

Inhibition of Kv2.1 Voltage-dependent K+Channels in Pancreatic β-Cells Enhances Glucose-dependent Insulin Secretion

The ATP- and tolbutamide-sensitivity of the ATP-sensitive K-channel from human pancreatic B cells

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