ATP-sensitive K+ channel effects on nerve function, Na+, K+ ATPase, and glutathione in diabetic rats

T C Hohman, M A Cotter, Norman E Cameron

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Some vasodilators correct nerve conduction velocity and endoneurial blood flow deficits in diabetic rats. It is not known whether vasa nervorum has ATP-sensitive K+ (K-ATP) channels that mediate vasodilation, or whether K-ATP channels could modulate peripheral nerve function. Therefore, we examined the effects of 2 weeks treatment with the K-ATP channel openers, celikalim and WAY135201 (R-4-[3, 4-dioxo-2-(1, 2, 2-trimethyl-propylamino)-cyclobut-1-1-enylamino]-3-methoxy-benzonitrile), on sciatic nerve blood flow, conduction velocity, Na+-K+ ATPase activity and glutathione content after 6 weeks of untreated streptozotocin-diabetes in rats. Blood flow and motor conduction velocity, 47.6% and 20.3% reduced by diabetes, respectively, were completely restored by both celikalim and WAY135201 treatments. Diabetes diminished sciatic Na+-K+ ATPase activity by 47.6% and this was 80-90% corrected by the K-ATP channel openers. Sciatic nerve glutathione content, 30.3% reduced by diabetes, was unaffected by celikalim or WAY135201. Thus, K-ATP channel openers had marked beneficial effects on nerve perfusion and function in experimental diabetic neuropathy, and may be suitable for further study in clinical trials. (C) 2000 Elsevier Science B.V. All rights reserved.

Original languageEnglish
Pages (from-to)335-341
Number of pages7
JournalEuropean Journal of Pharmacology
Volume397
Publication statusPublished - 2000

Keywords

  • nerve conduction
  • blood flow
  • K+ channel opener
  • Na+
  • K+ ATPase
  • oxidative stress
  • glutathione
  • neuropathy
  • diabetic rat
  • PROTEIN-KINASE-C
  • ALDOSE REDUCTASE INHIBITION
  • ENDONEURIAL BLOOD-FLOW
  • PERIPHERAL-NERVE
  • NITRIC-OXIDE
  • NEUROVASCULAR FUNCTION
  • CONDUCTION VELOCITY
  • POLYOL PATHWAY
  • OXYGEN-TENSION
  • LIPOIC ACID

Cite this

ATP-sensitive K+ channel effects on nerve function, Na+, K+ ATPase, and glutathione in diabetic rats. / Hohman, T C ; Cotter, M A ; Cameron, Norman E.

In: European Journal of Pharmacology, Vol. 397, 2000, p. 335-341.

Research output: Contribution to journalArticle

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AU - Cameron, Norman E

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N2 - Some vasodilators correct nerve conduction velocity and endoneurial blood flow deficits in diabetic rats. It is not known whether vasa nervorum has ATP-sensitive K+ (K-ATP) channels that mediate vasodilation, or whether K-ATP channels could modulate peripheral nerve function. Therefore, we examined the effects of 2 weeks treatment with the K-ATP channel openers, celikalim and WAY135201 (R-4-[3, 4-dioxo-2-(1, 2, 2-trimethyl-propylamino)-cyclobut-1-1-enylamino]-3-methoxy-benzonitrile), on sciatic nerve blood flow, conduction velocity, Na+-K+ ATPase activity and glutathione content after 6 weeks of untreated streptozotocin-diabetes in rats. Blood flow and motor conduction velocity, 47.6% and 20.3% reduced by diabetes, respectively, were completely restored by both celikalim and WAY135201 treatments. Diabetes diminished sciatic Na+-K+ ATPase activity by 47.6% and this was 80-90% corrected by the K-ATP channel openers. Sciatic nerve glutathione content, 30.3% reduced by diabetes, was unaffected by celikalim or WAY135201. Thus, K-ATP channel openers had marked beneficial effects on nerve perfusion and function in experimental diabetic neuropathy, and may be suitable for further study in clinical trials. (C) 2000 Elsevier Science B.V. All rights reserved.

AB - Some vasodilators correct nerve conduction velocity and endoneurial blood flow deficits in diabetic rats. It is not known whether vasa nervorum has ATP-sensitive K+ (K-ATP) channels that mediate vasodilation, or whether K-ATP channels could modulate peripheral nerve function. Therefore, we examined the effects of 2 weeks treatment with the K-ATP channel openers, celikalim and WAY135201 (R-4-[3, 4-dioxo-2-(1, 2, 2-trimethyl-propylamino)-cyclobut-1-1-enylamino]-3-methoxy-benzonitrile), on sciatic nerve blood flow, conduction velocity, Na+-K+ ATPase activity and glutathione content after 6 weeks of untreated streptozotocin-diabetes in rats. Blood flow and motor conduction velocity, 47.6% and 20.3% reduced by diabetes, respectively, were completely restored by both celikalim and WAY135201 treatments. Diabetes diminished sciatic Na+-K+ ATPase activity by 47.6% and this was 80-90% corrected by the K-ATP channel openers. Sciatic nerve glutathione content, 30.3% reduced by diabetes, was unaffected by celikalim or WAY135201. Thus, K-ATP channel openers had marked beneficial effects on nerve perfusion and function in experimental diabetic neuropathy, and may be suitable for further study in clinical trials. (C) 2000 Elsevier Science B.V. All rights reserved.

KW - nerve conduction

KW - blood flow

KW - K+ channel opener

KW - Na+

KW - K+ ATPase

KW - oxidative stress

KW - glutathione

KW - neuropathy

KW - diabetic rat

KW - PROTEIN-KINASE-C

KW - ALDOSE REDUCTASE INHIBITION

KW - ENDONEURIAL BLOOD-FLOW

KW - PERIPHERAL-NERVE

KW - NITRIC-OXIDE

KW - NEUROVASCULAR FUNCTION

KW - CONDUCTION VELOCITY

KW - POLYOL PATHWAY

KW - OXYGEN-TENSION

KW - LIPOIC ACID

M3 - Article

VL - 397

SP - 335

EP - 341

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

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