TY - JOUR
T1 - 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
AU - Ma, Ke Tao
AU - Guan, Bing Cai
AU - Yang, Yu Qin
AU - Zhao, Hui
AU - Jiang, Zhi Gen
N1 - Funding Information:
The project described was supported by Grant Number R01 DC004716 (to Z.G.J.) from the National Institute on Deafness and Other Communication Disorders. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Deafness and Other Communication Disorders or the National Institutes of Health. This work was also supported by a grant from the Deafness Research Foundation (to Z.G.J.) and by the National Natural Science Foundation of China, No. 30460043 (K.T.M.). The authors are grateful to Lauren Grimm, Jill Lilly and Dr. Takatoshi Karasawa for reading this manuscript.
PY - 2008/5
Y1 - 2008/5
N2 - 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 (Rinput) in high membrane potential (Vm) (∼-40 mV) cells but with no change or an increase in Rinput in low Vm (∼-75 mV) cells. ACh-depolarization was attenuated by background membrane depolarization from ∼-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 20 mM 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.
AB - 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 (Rinput) in high membrane potential (Vm) (∼-40 mV) cells but with no change or an increase in Rinput in low Vm (∼-75 mV) cells. ACh-depolarization was attenuated by background membrane depolarization from ∼-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 20 mM 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.
KW - Arteriole
KW - Intracellular recording
KW - Inward rectifier potassium channel
KW - Membrane potential
KW - TRP channel
KW - Whole-cell recording
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U2 - 10.1016/j.heares.2008.01.005
DO - 10.1016/j.heares.2008.01.005
M3 - Article
C2 - 18313244
AN - SCOPUS:42649132462
SN - 0378-5955
VL - 239
SP - 20
EP - 33
JO - Hearing Research
JF - Hearing Research
IS - 1-2
ER -