期刊
JOURNAL OF NEUROPHYSIOLOGY
卷 84, 期 5, 页码 2291-2301出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.2000.84.5.2291
关键词
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ATP-sensitive potassium (K-ATP) channels are heteromultimer complexes of subunits from members of the inwardly rectifying K+ channel and the ATP-binding cassette protein superfamilies. K-ATP channels couple metabolic state to membrane excitability, are distributed widely, and participate in a variety of physiological functions. Understood best in pancreatic beta cells, where their activation inhibits insulin release, K-ATP channels have been implicated also in postischemia cardio- and neuroprotection. The dentate gyrus (DG) is a brain region with a high density of K-ATP channels and is relatively resistant to ischemia/reperfusion-induced cell death. Therefore we were interested in describing the characteristics of single K-ATP channels in DG granule cells. We recorded single K-ATP channels in 59/105 cell-attached patches from DG granule cells in acutely prepared hippocampal slices. Single-channel openings had an E-K close to 0 mV (symmetrical K+) and were organized in bursts with a duration of 19.3 +/- 1.6 (SE) ms and a frequency of 3.5 +/- 0.8 Hz, a unitary slope conductance of 27 pS, and a low, voltage-independent, probability of opening (P-open, 0.04 +/- 0.01). Open and closed dwell-time histograms were fitted best with one ( tau (open) = 1.3 +/- 0.2 ms) and the sum of two ( tau (closed,fast) = 2.6 +/- 0.9 ms, tau (closed),(slow) = 302.7 +/- 67.7 ms) exponentials, respectively, consistent with a kinetic model having at least a single open and two closed states. The P-open was reduced ostensibly to zero by the sulfonylureas, glybenclamide (500 nM, 2/6; 10 muM,11/14 patches) and tolbutamide (20 muM, 4/6; 100 muM, 4/4 patches). The blocking dynamics for glybenclamide included transition to a subconductance state (43.3 +/- 2.6% of control I-open channel). Unlike glybenclamide, the blockade produced by tolbutamide was reversible. In 5/5 patches, application of diazoxide (100 muM) increased significantly P-open (0.12 +/- 0.02), which was attributable to a twofold increase in the frequency of bursts (8.3 +/- 2.0 Hz). Diazoxide was without effect on tau (open) and tau (closed), fast but decreased significantly tau (closed), (slow) (24.4 +/- 2.6 ms). We observed similar effects in 6/7 patches after exposure to hypoxia/hypoglycemia, which increased significantly P-open (0.09 +/- 0.03) and the frequency of bursts (7.1 +/- 1.7 Hz) and decreased significantly tau (closed, slow) (29.5 +/- 1.8 ms). We have presented convergent evidence consistent with single K-ATP channel activity in DG granule cells. The subunit composition of K-ATP channels native to DG granule cells is not known; however, the characteristics of the channel activity we recorded are representative of Kir6.1/SUR1, SUR2B-based channels.
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