Modulation of Three Types of Potassium Selective Channels by NAD and Other Pyridine Nucleotides in Human Pancreatic β-Cells
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ATP-regulated potassium (K+ATP) channels play a major role in control of the cell membrane potential in pancreatic β-cells, and therefore, nutrient-induced insulin secretion (for recent reviews see 1–4). It has been well documented that glucose-induced closure of these channels is involved in the initial depolarisation of the membrane(5), and widely accepted that this may occur through an increase in the intracellular ATP:ADP ratio which is responsible for coupling metabolic events to ionic events at the plasma membrane(1,2,4). However, other intracellular modulators of K+ATP channels could also be involved in the regulation of the complex cycles of electrical activity exhibited by the cells in response to glucose stimulation. Changes in the redox potential of the nicotine adenine dinucleotides NAD(P)/NAD(P)H have for many years been thought to be important intracellular signals that could mediate the effects of nutrient secretagogues on insulin secretion(6–9). In more recent studies it has been demonstrated using rodent β-cells stimulated with glucose that increases in the concentration of NAD(P)H occur prior to an increase in [Ca2+]i(10, 11), and also that all four of the pyridine nucleotides will modulate the gating of ATP-sensitive K+ channels in the RINm5F insulin-secreting cell line(12). Using patch clamp techniques we have now examined the effects of NAD and other pyridine nucleotides on the gating of three types of K+ channel in human pancreatic β-cells; the K+ATP channel, the Ca2+ and voltage gated channel, and a novel NAD-activated K+ channel.
KeywordsHuman Islet Pyridine Nucleotide Channel Inactivation RINm5F Cell United Kingdom Introduction
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