TY - JOUR
T1 - Basal nitric oxide production contributes to membrane potential and vasotone regulation of guinea pig in vitro spiral modiolar artery
AU - Jiang, Zhi Gen
AU - Shi, Xiaorui
AU - Zhao, Hui
AU - Si, Jun Qiang
AU - Nuttall, Alfred L.
N1 - Funding Information:
This work was supported by grants from the Deafness Research Foundation, Oregon Medical Research Foundation and NIH (NIDCD DC004716) (all to Z.-G.J.), and by NIH (NIDCD DC00105) and VA RR&D (RCTR 597-0160) (to A.L.N.).
PY - 2004/3
Y1 - 2004/3
N2 - Nitric oxide (NO) is a potent vasodilating agent implicated in cochlear blood flow regulation. We recently demonstrated that exogenously applied NO donor DPTA-NONOate hyperpolarizes both endothelial and smooth muscle cells of in vitro spiral modiolar artery (SMA) via activation of ATP-sensitive K + channels (KATP). Also, NO was detected in the SMA cells by NO indicator dye in the in vitro basal condition. Using intracellular recording techniques, electrochemical NO-sensing measurement, and a vaso-diameter video tracking method, we investigated the basal release of NO from the in vitro SMA and its role in the vascular function. We found that (1) 300 μM L-NAME, a NO synthase inhibitor, and 3 μM glipizide caused a depolarization of ∼4.5 and ∼3.2 mV, respectively, in cells with a resting potential less negative than -60 mV; (2) NO sensor in the close vicinity of the SMA detected a NO concentration of ∼50 nM that was suppressed by L-NAME and enhanced by L-arginine (1-1000 μM); (3) NO donor DPTA-NONOate (0.1-30 μM) applications produced about 8-245 nM of NO in the recording bath. These data indicate a NO concentration-hyperpolarization relation, with an EC50 of 22 nM. (4) Finally, L-NAME but not glipizide produced a 4.8% reduction in SMA diameter (∼50 μm) in the majority of SMAs, whereas NONOate (10 μM) always caused a dilation. Both the induced constriction and dilation were not significantly affected by 3 μM glipizide. We conclude that a significant amount of NO (>50 nM) is tonically released from the in vitro SMA, which is above the EC50 for activation of KATP, and thus contributes to the membrane polarization. The basal release of NO also contributes to vasotone relaxation, but the KATP activation appears to play little role in the relaxation of the in vitro SMA.
AB - Nitric oxide (NO) is a potent vasodilating agent implicated in cochlear blood flow regulation. We recently demonstrated that exogenously applied NO donor DPTA-NONOate hyperpolarizes both endothelial and smooth muscle cells of in vitro spiral modiolar artery (SMA) via activation of ATP-sensitive K + channels (KATP). Also, NO was detected in the SMA cells by NO indicator dye in the in vitro basal condition. Using intracellular recording techniques, electrochemical NO-sensing measurement, and a vaso-diameter video tracking method, we investigated the basal release of NO from the in vitro SMA and its role in the vascular function. We found that (1) 300 μM L-NAME, a NO synthase inhibitor, and 3 μM glipizide caused a depolarization of ∼4.5 and ∼3.2 mV, respectively, in cells with a resting potential less negative than -60 mV; (2) NO sensor in the close vicinity of the SMA detected a NO concentration of ∼50 nM that was suppressed by L-NAME and enhanced by L-arginine (1-1000 μM); (3) NO donor DPTA-NONOate (0.1-30 μM) applications produced about 8-245 nM of NO in the recording bath. These data indicate a NO concentration-hyperpolarization relation, with an EC50 of 22 nM. (4) Finally, L-NAME but not glipizide produced a 4.8% reduction in SMA diameter (∼50 μm) in the majority of SMAs, whereas NONOate (10 μM) always caused a dilation. Both the induced constriction and dilation were not significantly affected by 3 μM glipizide. We conclude that a significant amount of NO (>50 nM) is tonically released from the in vitro SMA, which is above the EC50 for activation of KATP, and thus contributes to the membrane polarization. The basal release of NO also contributes to vasotone relaxation, but the KATP activation appears to play little role in the relaxation of the in vitro SMA.
KW - Arteriole
KW - Cochlea
KW - NO release
KW - Nitric oxide synthase
KW - Potassium channel
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U2 - 10.1016/S0378-5955(03)00398-8
DO - 10.1016/S0378-5955(03)00398-8
M3 - Article
C2 - 14987756
AN - SCOPUS:1342329499
SN - 0378-5955
VL - 189
SP - 92
EP - 100
JO - Hearing Research
JF - Hearing Research
IS - 1-2
ER -