ACh-induced depolarization in inner ear artery is generated by activation of a TRP-like non-selective cation conductance and inactivation of a potassium conductance.

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  • Author(s): Ma KT;Ma KT; Guan BC; Yang YQ; Zhao H; Jiang ZG
  • Source:
    Hearing research [Hear Res] 2008 May; Vol. 239 (1-2), pp. 20-33. Date of Electronic Publication: 2008 Jan 20.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7900445 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0378-5955 (Print) Linking ISSN: 03785955 NLM ISO Abbreviation: Hear Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
    • Subject Terms:
      Membrane Potentials*; Acetylcholine/*metabolism ; Ear, Inner/*anatomy & histology ; Potassium/*chemistry; Amiloride/pharmacology ; Animals ; Anti-Inflammatory Agents/pharmacology ; Ear, Inner/metabolism ; Electric Conductivity ; Flufenamic Acid/pharmacology ; Guinea Pigs ; Indoles/pharmacology ; Myocytes, Smooth Muscle/metabolism ; Nifedipine/pharmacology ; Niflumic Acid/pharmacology ; Pyridines/pharmacology
    • Abstract:
      Adequate cochlear blood supply by the spiral modiolar artery (SMA) is critical for normal hearing. ACh may play a role in neuroregulation of the SMA but several key issues including its membrane action mechanisms remain poorly understood. Besides its well-known endothelium-dependent hyperpolarizing action, ACh can induce a depolarization in vascular cells. Using intracellular and whole-cell recording techniques on cells in guinea pig in vitro SMA, we studied the ionic mechanism underlying the ACh-depolarization and found that: (1) ACh induced a DAMP-sensitive depolarization when intermediate conductance KCa channels were blocked by charybdotoxin or nitrendipine. The ACh-depolarization was associated with a decrease in input resistance (R(input)) in high membrane potential (V(m)) ( approximately -40 mV) cells but with no change or an increase in R input in low Vm ( approximately -75 mV) cells. ACh-depolarization was attenuated by background membrane depolarization from approximately -70 mV in the majority of cells; (2) ACh-induced inward current in smooth muscle cells embedded in a SMA segment often showed a U-shaped I/V curve, the reversal potential of its two arms being near EK and 0 mV, respectively; (3) ACh-depolarization was reduced by low Na+, zero K+ or 20mM K+ bath solutions; (4) ACh-depolarization was inhibited by La3+ in all cells tested, by 4-AP and flufenamic acid in low Vm cells, but was not sensitive to Cd2+, Ni2+, nifedipine, niflumic acid, DIDS, IAA94, linopirdine or amiloride. We conclude that ACh-induced vascular depolarization was generated mainly by activation of a TRP-like non-selective cation channel and by inactivation of an inward rectifier K+ channel.
    • References:
      J Physiol. 1993 Jun;465:427-48. (PMID: 7693920)
      Hear Res. 1999 Dec;138(1-2):171-80. (PMID: 10575124)
      Pflugers Arch. 1999 Jul;438(2):187-94. (PMID: 10370105)
      Physiol Rev. 1989 Apr;69(2):546-604. (PMID: 2467318)
      Pharmacol Toxicol. 1994 Dec;75(6):327-36. (PMID: 7899253)
      J Physiol. 1988 Apr;398:277-89. (PMID: 2455799)
      Am J Physiol Heart Circ Physiol. 2002 Aug;283(2):H615-30. (PMID: 12124209)
      Methods Enzymol. 1992;207:100-22. (PMID: 1528114)
      Circ Res. 2001 Feb 16;88(3):325-32. (PMID: 11179201)
      Brain Res. 1981 Dec 14;229(1):203-8. (PMID: 7306809)
      J Physiol. 2001 Dec 15;537(Pt 3):829-42. (PMID: 11744758)
      J Physiol. 1993 Mar;462:529-45. (PMID: 8331591)
      Laryngoscope. 1972 Dec;82(12):2249-72. (PMID: 4539701)
      J Physiol. 1995 Sep 1;487 ( Pt 2):407-19. (PMID: 8558473)
      J Physiol. 1999 Apr 15;516 ( Pt 2):399-408. (PMID: 10087340)
      J Physiol. 2006 Dec 1;577(Pt 2):479-95. (PMID: 16973707)
      Pflugers Arch. 1988 Feb;411(2):137-46. (PMID: 3357753)
      Br J Pharmacol. 2007 Aug;151(7):1049-60. (PMID: 17572704)
      Am J Physiol. 1996 Aug;271(2 Pt 2):H696-705. (PMID: 8770113)
      Science. 1980 Aug 29;209(4460):976-83. (PMID: 6157191)
      J Physiol. 1996 Aug 1;494 ( Pt 3):715-26. (PMID: 8865069)
      Proc Natl Acad Sci U S A. 2002 May 28;99(11):7461-6. (PMID: 12032305)
      Cell Calcium. 2006 Jul;40(1):29-40. (PMID: 16697039)
      Noise Health. 1999;2(5):17-32. (PMID: 12689482)
      Circ Res. 2006 Jul 21;99(2):119-31. (PMID: 16857972)
      Acta Pharmacol Sin. 2006 Jul;27(7):833-42. (PMID: 16787566)
      J Physiol. 2007 May 1;580(Pt.3):755-64. (PMID: 17303636)
      Am J Otolaryngol. 1988 Nov-Dec;9(6):317-22. (PMID: 3067594)
      J Neurophysiol. 2007 May;97(5):3432-8. (PMID: 17376848)
      J Pharmacol Exp Ther. 1991 Sep;258(3):842-50. (PMID: 1716312)
      Hear Res. 2002 Sep;171(1-2):167-176. (PMID: 12204360)
      Trends Pharmacol Sci. 2002 Aug;23(8):374-80. (PMID: 12377579)
      Science. 1982 Aug 20;217(4561):739-41. (PMID: 6179162)
      J Pharmacol Exp Ther. 2007 Feb;320(2):544-51. (PMID: 17082310)
      Br Med Bull. 2002;63:195-212. (PMID: 12324394)
      J Physiol. 1992 Sep;455:471-85. (PMID: 1484360)
      Microcirculation. 2005 Jan-Feb;12(1):113-27. (PMID: 15804979)
      Nature. 2003 Dec 4;426(6966):517-24. (PMID: 14654832)
      Am J Physiol. 1995 Apr;268(4 Pt 1):C799-822. (PMID: 7733230)
      Cell. 2007 Apr 6;129(1):220. (PMID: 17418797)
      Am J Physiol Cell Physiol. 2002 Feb;282(2):C347-59. (PMID: 11788346)
      J Physiol. 2004 Dec 1;561(Pt 2):415-32. (PMID: 15579537)
      J Physiol. 2006 Jan 1;570(Pt 1):45-51. (PMID: 16195316)
      Am J Otolaryngol. 1982 Sep-Oct;3(5):349-52. (PMID: 7149147)
      Am J Otolaryngol. 1988 Nov-Dec;9(6):278-90. (PMID: 3067591)
      J Physiol. 2003 May 15;549(Pt 1):143-56. (PMID: 12679370)
      Br J Pharmacol. 2004 Mar;141(6):881-903. (PMID: 15028638)
      J Physiol. 2005 Apr 15;564(Pt 2):475-87. (PMID: 15731195)
      J Physiol. 2006 Mar 1;571(Pt 2):361-9. (PMID: 16396924)
      J Neurochem. 1995 Sep;65(3):1274-81. (PMID: 7543933)
      J Hypertens. 2007 Feb;25(2):345-59. (PMID: 17211241)
    • Grant Information:
      R01 DC004716 United States DC NIDCD NIH HHS; R01 DC004716-01A2 United States DC NIDCD NIH HHS; R01 DC004716-05 United States DC NIDCD NIH HHS; R01 DC004716-02 United States DC NIDCD NIH HHS; R01 DC004716-04 United States DC NIDCD NIH HHS; R01 DC004716-03 United States DC NIDCD NIH HHS
    • Accession Number:
      0 (Anti-Inflammatory Agents)
      0 (Indoles)
      0 (Pyridines)
      4U5MP5IUD8 (Niflumic Acid)
      60GCX7Y6BH (Flufenamic Acid)
      7DZO8EB0Z3 (Amiloride)
      I5TB3NZ94T (linopirdine)
      I9ZF7L6G2L (Nifedipine)
      N9YNS0M02X (Acetylcholine)
      RWP5GA015D (Potassium)
    • Publication Date:
      Date Created: 20080304 Date Completed: 20080709 Latest Revision: 20211020
    • Publication Date:
      20231215
    • Accession Number:
      PMC2443412
    • Accession Number:
      10.1016/j.heares.2008.01.005
    • Accession Number:
      18313244