title: 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.
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.
authors.affiliation: Oregon Hearing Research Center, Department of Otolaryngology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Ke-Tao
authors.initials: KT
authors.lastname: Ma
authors.forename: Bing-Cai
authors.initials: BC
authors.lastname: Guan
authors.forename: Yu-Qin
authors.initials: YQ
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Zhi-Gen
authors.initials: ZG
authors.lastname: Jiang
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D007758:Ear, Inner / Q000033:anatomy & histology* / Q000378:metabolism; D004553:Electric Conductivity; D005439:Flufenamic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D008564:Membrane Potentials; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009544:Niflumic Acid / Q000494:pharmacology; D011188:Potassium / Q000737:chemistry*; D011725:Pyridines / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D007211:Indoles; D011725:Pyridines; D009544:Niflumic Acid; D005439:Flufenamic Acid; D000584:Amiloride; C061017:linopirdine; D009543:Nifedipine; D000109:Acetylcholine; D011188:Potassium