Effects of local anesthetics and related drugs on endogenous glibenclamide-sensitive K+ channels in Xenopus oocytes

Yoneda, Ikuo; Sakuta, Hidenari; Okamoto, Koichi; Watanabe, Yasuhiro

doi:10.1016/0922-4106(93)90194-e

Cited by 17 publications

(7 citation statements)

References 27 publications

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“…Tetracaine, however, has minimal effects on membrane potential in isolated rat soleus (Clausen and Flatman 1977). Tetracaine also reversibly blocks the cardiac SR Ca 2+ release channel (Smith and O'Neill 2001) and, at high concentrations (IC 50 845 µM), inhibits glibenclamide-sensitive K + (K ATP ) channels in Xenopus laevis oocytes (Yoneda et al 1993). Finally, because the concentrations of glycoside exerting an increased unidirectional efflux of K + in the present study are greater than therapeutic plasma concentrations in humans, it remains to be determined if there is a physiologi-cally significant effect of ouabain on skeletal muscle K + efflux in vivo.…”

Section: Discussionmentioning

confidence: 99%

Ouabain stimulates unidirectional and net potassium efflux in resting mammalian skeletal muscle

Hawke

Lessard²,

Vickery³

et al. 2001

Can. J. Physiol. Pharmacol.

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The present study compared ouabain-sensitive unidirectional K+ flux into (JinK) and out of (JoutK) perfused rat hindlimb skeletal muscle in situ and mouse flexor digitorum brevis (FDB) in vitro. In situ, 5 mM ouabain inhibited 54 +/- 4% of the total JinK in 28 +/- 1 min, and increased the net and unidirectional efflux of K+ within 4 min. In contrast, 1.8 mM ouabain inhibited 40 +/- 8% of the total JinK in 38 +/- 2 min, but did not significantly affect JoutK. In vitro, 1.8 and 0.2 mM ouabain decreased JinK to a greater extent (83 +/- 5%) than in situ, but did not significantly affect 42K loss rate compared with controls. The increase in unidirectional K+ efflux (JoutK) with 5 mM ouabain in situ was attributed to increased K+ efflux through cation channels, since addition of barium (1 mM) to ouabain-perfused muscles returned JoutK to baseline values within 12 min. Perfusion with 5 mM ouabain plus 2 mM tetracaine for 30 min decreased JinK 46 +/- 9% (0.30 +/- 0.03 to 0.16 +/- 0.02 micromol x min(-1) x g(-1)), however tetracaine was unable to abolish the ouabain-induced increase in unidirectional K+ efflux. In both rat hindlimb and mouse FDB, tetracaine had no effect on JoutK. Perfusion of hindlimb muscle with 0.1 mM tetrodotoxin (TTX, a Na+ channel blocker) decreased JinK by 15 +/- 1%, but had no effect on JoutK; subsequent addition of ouabain (5 mM) decreased JinK a further 32 +/- 2%. The ouabain-induced increase in unidirectional K+ efflux did not occur when TTX was perfused prior to and during perfusion with 5 mM ouabain. We conclude that 5 mM ouabain increases the unidirectional efflux of K+ from skeletal muscle through a barium and TTX-sensitive pathway, suggestive of voltage sensitive Na+ channels, in addition to inhibiting Na+/K+-ATPase activity.

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Section: Discussionmentioning

confidence: 99%

Ouabain stimulates unidirectional and net potassium efflux in resting mammalian skeletal muscle

Hawke

Lessard²,

Vickery³

et al. 2001

Can. J. Physiol. Pharmacol.

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“…Local anesthetics inhibit voltage gated calcium and potassium channels [27, 28]and ATP-sensitive potassium channels [29]. Local anesthetics have inhibitory effects on G-protein coupled receptors such as thromboxane A 2 [30], M 1 and M 3 muscarinic [31, 32]and LPA [33]receptors.…”

Section: Discussionmentioning

confidence: 99%

Local Anesthetics Induce Human Renal Cell Apoptosis

Lee¹,

Xu²,

Siegel³

et al. 2003

Am J Nephrol

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Renal cell apoptosis contributes significantly to the pathogenesis of acute renal failure. Local anesthetics induce apoptosis in neuronal and lymphocytic cell lines. We examined the effects of chronic (48 h) local anesthetic treatment (lidocaine, bupivacaine and tetracaine) on human proximal tubular (HK-2) cells. Apoptosis induction was assessed by detecting poly(ADP)-ribose polymerase fragmentation, caspase activation, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining, DNA laddering and by cellular morphology. Cell death was quantified by measuring neutral red dye uptake and lactate dehydrogenase released into the cell culture medium. All 3 local anesthetics caused concentration-dependent cell death, induced HK-2 cell apoptosis and potentiated TNF-α induced apoptosis. Local anesthetics induced HK-2 cell apoptosis by activation of caspases 3, 6, 7, 8 and 9. ZVAD-fmk, a pan-caspase inhibitor, blocked the local anesthetic induced HK-2 cell apoptosis. Local anesthetics also inhibited the activities of anti-apoptotic kinases protein kinase B (Akt) and extracellular signal regulated mitrogen-activated protein kinase. Local anesthetic’s pro-apoptotic effects are independent of sodium channel inhibition as tetrodotoxin, a selective voltage-gated sodium channel blocker, failed to mimic local anesthetic-mediated induction or potentiation of HK-2 cell apoptosis. We conclude that local anesthetics induce human renal cell apoptotic signaling by caspase activation and via inhibition of pro-survival signaling pathways.

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“…Other local anaesthetic agents such as tetracaine, dibucaine, benoxinate, procaine and bupivacaine also inhibited IL-5-evoked eosinophil survival in vitro but their pro-apoptotic performance did not reflect their respective anaesthetic potencies . It is well established that lidocaine at high concentrations can also block K + channels (Illek et al 1992, Yoneda et al 1993, Olschewski et al 1996. Therefore, Bankers-Fulbright and coworkers studied the effect of three classes of K+ channel blockers and reported that the sulfonylureas including glyburide, tolbutamide, and glipizide (one class of K+ channel blockers) were the only ones able to mimic the effect of lidocaine on the inhibition of cytokine-mediated eosinophil survival and superoxide production in vitro.…”

Section: Local Anaesthetics and Allergic Inflammationmentioning

confidence: 99%