Abstract
Aim:
The influence of niflumic acid (NFA), a Cl− channel antagonist, on the membrane potentials in smooth muscle cells (SMC) of the cochlear spiral modiolar artery (SMA) in guinea pigs was examined.
Methods:
The intracellular recording and whole-cell recording technique were used to record the NFA-induced response on the acutely-isolated SMA preparation.
Results:
The SMC had 2 stable but mutually convertible levels of resting potentials (RP), that is, one was near −45 mV and the other was approximately −75 mV, termed as low and high RP, respectively. The bath application of NFA could cause a hyperpolarization in all the low RP cells, but had little effect on high RP cells. The induced responses were concentration-dependent. Large concentrations of NFA (≥100 μmol/L) often induced a shift of a low RP to high RP in cells with an initial RP at low level, and NFA (up to 100 μmol/L) had little effect on the membrane potentials of the high RP cells. However, when the high RP cells were depolarized to a level beyond −45 mV by barium and ouabain, NFA hyperpolarized these cells with the similar effect on those cells initially being the low RP. The NFA-induced response was almost completely blocked by charybdotoxin, iberiotoxin, tetraethylammonium, 1,2-bis(2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid tetrakis acetoxymethyl ester, but not by 4-aminopyridine, barium, glipizide, apamin, ouabain, and CdCl2.
Conclusion:
NFA induces a concentration-dependent reversible hyperpolarization in SMC in the cochlear SMA via activation of the Ca2+-activated potassium channels.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Thorne PR, Nuttall AL, Scheibe F, Miller JM . Sound-induced artifact in cochlear blood flow measurements using the laser Doppler flowmeter. Hear Res 1987; 31: 229–34.
Ren T, Brown NJ, Zhang M, Nuttall AL, Miller JM . A reversible ischemia model in gerbil cochlea. Hear Res 1995; 92: 30–7.
Hultcrantz E . Clinical treatment of vascular inner ear diseases. Am J Otolaryngol 1988; 9: 317–22.
Nuttall AL, Hultcrantz E, Larsen HC, Angelborg C . Cochlear blood flow increases after systemic hemodilution: comparison of simultaneous laser Doppler flowmetry and radioactive microsphere measurements. Hear Res 1988; 34: 215–23.
Didier A, Miller JM, Nuttall AL . The vascular component of sodium salicylate ototoxicity in the guinea pig. Hear Res 1993; 69: 199–206.
Tamhankar M, Solomon D . Acute Hearing Loss. Curr Treat Options Neurol 2004; 6: 55–65.
Beech DJ, Bolton TB . Two components of potassium current activated by depolarization of single smooth muscle cells from the rabbit portal vein. J Physiol 1989; 418: 293–309.
Latorre R, Oberhauser A, Labarca P, Alvarez O . Varieties of calcium-activated potassium channels. Annu Rev Physiol 1989; 51: 385–99.
Kovacs RJ, Nelson MT . ATP-sensitive K+ channels from aortic smooth muscle incorporated into planar lipid bilayers. Am J Physiol 1991; 261 ( 2 Pt 2): H604–9.
McManus OB . Calcium-activated potassium channels: regulation by calcium. J Bioenerg Biomembr 1991; 23: 537–60.
Quayle JM, McCarron JG, Brayden JE, Nelson MT . Inward rectifier K+ currents in smooth muscle cells from rat resistance-sized cerebral arteries. Am J Physiol 1993; 265 ( 5 Pt 1): C1363–70.
Jiang ZG, Nuttall AL, Zhao H, Dai CF, Guan BC, Si JQ, et al. Electrical coupling and release of K+ from endothelial cells comediate ACh-induced smooth muscle hyperpolarization in guinea-pig inner ear artery. J Physiol 2005; 564 ( Pt 2): 475–87.
Crest M, Gola M . Large conductance Ca(2+)-activated K+ channels are involved in both spike shaping and firing regulation in helix neurones. J Physiol 1993, 465: 265–87.
Gola M, Crest M . Colocalization of active KCa channels and Ca2+ channels within Ca2+ domains in helix neurons. Neuron 1993; 10: 689–99.
Brayden JE, Nelson MT . Regulation of arterial tone by activation of calcium-dependent potassium channels. Science 1992; 256: 532–5.
Suarez-Kurtz G, Garcia ML, Kaczorowski GJ . Effects of charybdotoxin and iberiotoxin on the spontaneous motility and tonus of different guinea pig smooth muscle tissues. J Pharmacol Exp Ther 1991; 259: 439–43.
Anwer K, Oberti C, Perez GJ, Perez-Reyes N, McDougall JK, Monga M, et al. Calcium-activated K+ channels as modulators of human myometrial contractile activity. Am J Physiol 1993; 265 ( 4 Pt 1): C976–85.
Khan SA, Mathews WR, Meisheri KD . Role of calcium-activated K+ channels in vasodilation induced by nitroglycerine, acetyl-choline and nitric oxide. J Pharmacol Exp Ther 1993; 267: 1327–35.
White MM, Aylwin M . Niflumic and flufenamic acids are potent reversible blockers of Ca2(+)-activated Cl- channels in Xenopus oocytes. Mol Pharmacol 1990; 37: 720–4.
Korn SJ, Bolden A, Horn R . Control of action potentials and Ca2+ influx by the Ca(2+)-dependent chloride current in mouse pituitary cells. J Physiol 1991; 439: 423–37.
McCarty NA, McDonough S, Cohen BN, Riordan JR, Davidson N, Lester HA . Voltage-dependent block of the cystic fibrosis transmembrane conductance regulator Cl- channel by two closely related arylaminobenzoates. J Gen Physiol 1993; 102: 1–23.
Greenwood IA, Large WA . Comparison of the effects of fenamates on Ca-activated chloride and potassium currents in rabbit portal vein smooth muscle cells. Br J Pharmacol 1995; 116: 2939–48.
Ottolia M, Toro L . Potentiation of large conductance KCa channels by niflumic, flufenamic, and mefenamic acids. Biophys J 1994; 67: 2272–9.
Wang YZ, Liu ZJ, Li L, Fan P, Si JQ, Zhao L, et al. Effects of chloride channel blockers on excitatory junction potentials in smooth muscle cells of cochlear spiral modiolar artery in guinea pigs. Sheng Li Xue Bao 2006; 58: 456–62.
Si JQ, Zhao H, Yang Y, Jiang ZG, Nuttall AL . Nitric oxide induces hyperpolarization by opening ATP-sensitive K(+) channels in guinea pig spiral modiolar artery. Hear Res 2002, 171: 167–76.
Jiang ZG, Si JQ, Lasarev MR, Nuttall AL . Two resting potential levels regulated by the inward-rectifier potassium channel in the guinea-pig spiral modiolar artery. J Physiol 2001; 537 ( Pt 3): 829–42.
Guan BC, Si JQ, Jiang ZG . Blockade of gap junction coupling by glycyrrhetinic acids in guinea pig cochlear artery: a whole-cell voltage- and current-clamp study. Br J Pharmacol 2007; 151: 1049–60.
Knot HJ, Zimmermann PA, Nelson MT . Extracellular K(+)-induced hyperpolarizations and dilatations of rat coronary and cerebral arteries involve inward rectifier K(+) channels. J Physiol 1996; 492: 419–30.
Robertson BE, Nelson MT . Aminopyridine inhibition and voltage dependence of K+ currents in smooth muscle cells from cerebral arteries. Am J Physiol 1994; 267 ( 6 Pt 1): C1589–97.
Rae JL, Farrugia G . Whole-cell potassium current in rabbit corneal epithelium activated by fenamates. J Membr Biol 1992; 129: 81–97.
Farrugia G, Rae JL, Szurszewski JH . Characterization of an outward potassium current in canine jejunal circular smooth muscle and its activation by fenamates. J Physiol 1993; 468: 297–310.
Farrugia G, Rae JL, Sarr MG, Szurszewski JH . Potassium current in circular smooth muscle of human jejunum activated by fenamates. Am J Physiol 1993; 265 ( 5 Pt 1): G873–9.
Rudy B . Diversity and ubiquity of K channels. Neuroscience 1988; 25: 729–49.
Sah P . Ca(2+)-activated K+ currents in neurones: types, physiological roles and modulation. Trends Neurosci 1996; 19: 150–4.
Nilius B, Droogmans G . Ion channels and their functional role in vascular endothelium. Physiol Rev 2001; 81: 1415–59.
Jiang ZG, Qiu J, Ren T, Nuttall AL . Membrane properties and the excitatory junction potentials in smooth muscle cells of cochlear spiral modiolar artery in guinea pigs. Hear Res 1999; 138: 171–80.
Jiang ZG, Shi X, Zhao H, Si JQ, Nuttall AL . Basal nitric oxide production contributes to membrane potential and vasotone regulation of guinea pig in vitro spiral modiolar artery. Hear Res 2004; 189: 92–100.
Farley J, Rudy B . Multiple types of voltage-dependent Ca2+-activated K+ channels of large conductance in rat brain synaptosomal membranes. Biophys J 1988; 53: 919–34.
Inoue R, Kitamura K, Kuriyama H . Two Ca-dependent K-channels classified by the application of tetraethylammonium distribute to smooth muscle membranes of the rabbit portal vein. Pflugers Arch 1985; 405: 173–9.
Reinhart PH, Chung S, Levitan IB . A family of calcium-dependent potassium channels from rat brain. Neuron 1989; 2: 1031–41.
Kozak JA, Misler S, Logothetis DE . Characterization of a Ca2+-activated K+ current in insulin-secreting murine betaTC-3 cells. J Physiol 1998; 509 ( Pt 2): 355–70.
Jury J, Patel M, Bowes T, Daniel EE . Actions of putative chloride channel blocking agents on canine lower esophageal sphincter (LES). Can J Physiol Pharmacol 2001; 79: 1007–14.
Poronnik P, Ward MC, Cook DI . Intracellular Ca2+ release by flufenamic acid and other blockers of the non-selective cation channel. FEBS Lett 1992; 296: 245–8.
Greenwood IA, Leblanc N . Overlapping pharmacology of Ca2+-activated Cl- and K+ channels. Trends Pharmacol Sci 2007; 28: 1–5.
Edwards G, Dora KA, Gardener MJ, Garland CJ, Weston AH . K+ is an endothelium-derived hyperpolarizing factor in rat arteries. Nature 1998; 396: 269–72.
Weston AH, Richards GR, Burnham MP, Feletou M, Vanhoutte PM, Edwards G . K+-induced hyperpolarization in rat mesenteric artery: identification, localization and role of Na+/K+-ATPases. Br J Pharmacol 2002; 136: 918–26.
Edwards G, Feletou M, Gardener MJ, Thollon C, Vanhoutte PM, Weston AH . Role of gap junctions in the responses to EDHF in rat and guinea-pig small arteries. Br J Pharmacol 1999; 128: 1788–94.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by the National Natural Science Foundation of China (No 30460043); the Scientific and Technological Program for Overseas Personnel, the Ministry of Personnel, China (2006); and the Key Program of Scientific and Technological Research, the Ministry of Education, China (Local Universities; No 207134).
Rights and permissions
About this article
Cite this article
Li, L., Ma, Kt., Zhao, L. et al. Niflumic acid hyperpolarizes smooth muscle cells via calcium-activated potassium channel in spiral modiolar artery of guinea pigs. Acta Pharmacol Sin 29, 789–799 (2008). https://doi.org/10.1111/j.1745-7254.2008.00803.x
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1111/j.1745-7254.2008.00803.x
Keywords
This article is cited by
-
Possible teleconnections between East and South Asian summer monsoon precipitation in projected future climate change
Meteorology and Atmospheric Physics (2019)
-
Characterizing effects of monsoons and climate teleconnections on precipitation in China using wavelet coherence and global coherence
Climate Dynamics (2019)
-
Possible mechanism for the weakening relationship between Indian and central East Asian summer rainfall after the late 1970s: role of the mid-to-high-latitude atmospheric circulation
Meteorology and Atmospheric Physics (2019)
-
Differential effect of calcium-activated potassium and chloride channels on rat basilar artery vasomotion
Journal of Huazhong University of Science and Technology [Medical Sciences] (2014)
-
Niflumic Acid Affects Store-Operated Ca2+-Permeable (SOC) and Ca2+-Dependent K+ and Cl− Ion Channels and Induces Apoptosis in K562 Cells
The Journal of Membrane Biology (2014)
