| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
ATP-sensitive K^+ (K_<ATP>) channels, which represent a family of K^+ channels inhibited by intracellular ATP, have been found in a variety of tissues including heart, pancreatic beta-cells, skeletal muscle, smooth muscle, and the central nervous system.These K_<ATP> channels are closely related to diverse cellular functions, such as shortening of action potential duration and cellular loss of K^+ ions that occur during metabolic inhibition in heart, insulin secretion from pancreatic beta-cells, smooth muscle relaxation, regulation of skeletal muscle excitability, and neurotransmitter release.Furthermore, other diverse factors such as NDP, pH, Mg^<2+>, polyamine, PIP_2, G proteins, K^+ channel openers and sulfonylurea also modulate the activity of K_<ATP> channels.K_<ATP> channel is composed of two kinds of membrane proteins Kir6.x and SURx.We characterized K_<ATP> channels reconstituted with various combination of subunits expressed in mammalian cell line with patch clamp techniques.The result runs as follows ; 1) The activity of K_<ATP> channel with Kir6.2 and SUR2A is almost same as that of cardiac K_<ATP> channel.2) Spontaneous openings and unitary conductances of Kir6.1 and Kir6.2 are determined with a part of each N- and C-terminus and extracellular linker domain between the two putative membrane-spanning regions, respectively.3) Splicing isoforms of SUR2A and SUR2B which are divergent at C terminus have different sensitivities to both K^+ channel openers and sulfonylurea.4) Although SUR subunits contain the critical binding sites for K^+ channel openers and intracellular nucleotides, the Kir subunits seem to influence the way in which the entire SUR/Kir functional channel complex reacts to these compounds.
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