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    Glucose reduces endothelin inhibition of voltage-gated potassium channels in rat arterial smooth muscle cells

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    Publication date
    2006-09
    Author
    Rainbow, R.D.
    Hardy, Matthew E.
    Standen, N.B.
    Davies, N.W.
    Keyword
    Endothelin-1 (ET-1)
    Arterial smooth muscle cells
    Voltage-gated K+ current (IKV) inhibition
    Peer-Reviewed
    yes
    
    Metadata
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    Abstract
    Prolonged 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.
    URI
    http://hdl.handle.net/10454/16508
    Version
    No full-text in the repository
    Citation
    Rainbow 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.
    Link to publisher’s version
    https://doi.org/10.1113/jphysiol.2006.114009
    Type
    Article
    Collections
    Life Sciences Publications

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