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dc.contributor.authorRainbow, R.D.*
dc.contributor.authorHardy, Matthew E.*
dc.contributor.authorStanden, N.B.*
dc.contributor.authorDavies, N.W.*
dc.date.accessioned2018-07-25T11:20:49Z
dc.date.available2018-07-25T11:20:49Z
dc.date.issued2006-09
dc.identifier.citationRainbow RD, Hardy ME, Standen NB and Davies NW (2006) Glucose reduces endothelin inhibition of voltage-gated potassium channels in rat arterial smooth muscle cells. Journal of Physiology. 575 (3): 833-44.en_US
dc.identifier.urihttp://hdl.handle.net/10454/16508
dc.descriptionnoen_US
dc.description.abstractProlonged hyperglycaemia impairs vascular reactivity and inhibits voltage-activated K+ (Kv) channels. We examined acute effects of altering glucose concentration on the activity and inhibition by endothelin-1 (ET-1) of Kv currents of freshly isolated rat arterial myocytes. Peak Kv currents recorded in glucose-free solution were reversibly reduced within 200 s by increasing extracellular glucose to 4 mm. This inhibitory effect of glucose was abolished by protein kinase C inhibitor peptide (PKC-IP), and Kv currents were further reduced in 10 mm glucose. In current-clamped cells, membrane potentials were more negative in 4 than in 10 mm glucose. In 4 mmd-glucose, 10 nm ET-1 decreased peak Kv current amplitude at +60 mV from 23.5 ± 3.3 to 12.1 ± 3.1 pA pF−1 (n = 6, P < 0.001) and increased the rate of inactivation, decreasing the time constant around fourfold. Inhibition by ET-1 was prevented by PKC-IP. When d-glucose was increased to 10 mm, ET-1 no longer inhibited Kv current (n = 6). Glucose metabolism was required for prevention of ET-1 inhibition of Kv currents, since fructose mimicked the effects of d-glucose, while l-glucose, sucrose or mannitol were without effect. Endothelin receptors were still functional in 10 mmd-glucose, since pinacidil-activated ATP-dependent K+ (KATP) currents were reduced by 10 nm ET-1. This inhibition was nearly abolished by PKC-IP, indicating that endothelin receptors could still activate PKC in 10 mmd-glucose. These results indicate that changes in extracellular glucose concentration within the physiological range can reduce Kv current amplitude and can have major effects on Kv channel modulation by vasoconstrictors.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1113/jphysiol.2006.114009en_US
dc.subjectEndothelin-1 (ET-1)en_US
dc.subjectArterial smooth muscle cellsen_US
dc.subjectVoltage-gated K+ current (IKV) inhibitionen_US
dc.titleGlucose reduces endothelin inhibition of voltage-gated potassium channels in rat arterial smooth muscle cellsen_US
dc.status.refereedyesen_US
dc.typeArticleen_US
dc.type.versionNo full-text in the repositoryen_US


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