Expression and Function of Pancreatic β-Cell Delayed Rectifier K+ Channels

Abstract

Voltage-dependent delayed rectifier K؉ channels regulate aspects of both stimulus-secretion and excitationcontraction coupling, but assigning specific roles to these channels has proved problematic. Using transgenically derived insulinoma cells (␤TC3-neo) and ␤-cells purified from rodent pancreatic islets of Langerhans, we studied the expression and role of delayed rectifiers in glucose-stimulated insulin secretion.

Voltage-dependent K+ channels are positive regulators of alpha cell action potential generation and glucagon secretion in mice and humans

“…This would be similar to the well-known effect of inhibiting beta cell Kv currents on insulin secretion, even with very high concentrations (20 mmol/l) of TEA [11,16,20]. We found that alpha cell Kv currents are inhibited by low millimolar levels of TEA and 4-aminopyridine.…”

“…Notably, we did not observe the TEA-resistant rapidly inactivating current component reported previously in isolated alpha cells [19] and alpha cells from intact islets [3]. In beta cells, inhibition of Kv currents with TEA augments insulin secretion in a glucose-dependent manner, since Kv channels contribute to action potential repolarisation [11,16,20]. Since alpha cells are electrically active at low glucose [3,4,21], we hypothesised that inhibition of Kv currents at low glucose concentrations should enhance glucagon secretion under this condition, due to action potential prolongation as is the case for beta cell insulin secretion.…”

“…It is unlikely that suppression of glucagon secretion under these conditions is mediated by paracrine inhibition via beta cell secretory products. While TEA enhances glucosedependent insulin secretion, the concentrations used here are well below the EC 50 for stimulation of insulin secretion from rodent islets (8.24 mmol/l) [11] and TEA is well known to have no beta cell stimulatory effect at low glucose [11,20]. Therefore, it is likely that TEA acts directly on alpha cells to suppress glucagon secretion.…”

Mechanisms of action of glucagon-like peptide 1 in the pancreas

“…A summary of expression the various K v families in insulinoma cells and rat islets has been compiled by . In the resting β cell the K v channels are closed and they open in response to membrane depolarization following glucose-induced insulin secretion (Roe et al, 1996). In relation to insulin secretion the effects of the K v2.1 channel has been the one most studied in cellular models as it possibly is the major contributor to the voltagedependent outward K + current.…”

Modulation of the Pancreatic Islet β-Cell-delayed Rectifier Potassium Channel Kv2.1 by the Polyunsaturated Fatty Acid Arachidonate

“…Changes in the relative concentrations of the metabolites ATP and ADP cause ␤-cell depolarization via closure of ATP-sensitive potassium channels (K ATP ), 3 which results in activation of voltage-operated Ca 2ϩ channels, Ca 2ϩ influx, and insulin secretion (1). The extent of ␤-cell depolarization and insulin release are regulated in part by the activation of repolarizing ion channels, including the voltage-gated potassium channel, Kv2.1 (2)(3)(4). One mechanism employed by pancreatic ␤-cells to regulate the biophysical activity of the ion channels involved in insulin release involves hydrolysis of membrane phospholipids to yield mediators that include inositol triphosphates and free fatty acids (5)(6)(7)(8).…”