TY - JOUR
T1 - Diverse Kir expression contributes to distinct bimodal distribution of resting potentials and vasotone responses of arterioles
AU - Yang, Yuqin
AU - Chen, Fangyi
AU - Karasawa, Takatoshi
AU - Ma, Ke Tao
AU - Guan, Bing Cai
AU - Shi, Xiao Rui
AU - Li, Hongzhe
AU - Steyger, Peter
AU - Nuttall, Alfred L.
AU - Jiang, Zhi-Gen
N1 - Funding Information:
We are grateful to Edward Porsov for development of vessel edge detection software. This work was supported by grants from Hearing Health Foundation (ZGJ), Oregon Medical Research Fund (ZGJ), National Institute of Health National Institute on Deafness and other Communication Disorders (NIH NIDCD) R01 DC004716 (ZGJ), and by NIH NIDCD R03DC011622 (HL), DC010844 (XS), DC R21DC1239801 (XS), DC004555 (PSS), DC00105 (ALN) and NIH P30 DC005983.
Publisher Copyright:
© 2015 Yang et al.
PY - 2015/5/4
Y1 - 2015/5/4
N2 - The resting membrane potential (RP) of vascular smooth muscle cells (VSMCs) is a major determinant of cytosolic calcium concentration and vascular tone. The heterogeneity of RPs and its underlying mechanism among different vascular beds remain poorly understood. We compared the RPs and vasomotion properties between the guinea pig spiral modiolar artery (SMA), brain arterioles (BA) and mesenteric arteries (MA). We found: 1) RPs showed a robust bimodal distribution peaked at -76 and -40 mV evenly in the SMA, unevenly at -77 and -51 mV in the BA and ∼-71 and -52 mV in the MA. Ba2+ 0.1 mM eliminated their high RP peaks ∼-75 mV. 2) Cells with low RP (∼-45 mV) hyperpolarized in response to 10 mM extracellular K+, while cells with a high RP depolarized, and cells with intermediate RP (∼-58 mV) displayed an initial hyperpolarization followed by prolonged depolarization. Moderate high K+ typically induced dilation, constriction and a dilation followed by constriction in the SMA, MA and BA, respectively. 3) Boltzmann-fit analysis of the Ba2+-sensitive inward rectifier K+ (Kir) whole-cell current showed that the maximum Kir conductance density significantly differed among the vessels, and the half-activation voltage was significantly more negative in the MA. 4) Corresponding to the whole-cell data, computational modeling simulated the three RP distribution patterns and the dynamics of RP changes obtained experimentally, including the regenerative swift shifts between the two RP levels after reaching a threshold. 5) Molecular works revealed strong Kir2.1 and Kir2.2 transcripts and Kir2.1 immunolabeling in all 3 vessels, while Kir2.3 and Kir2.4 transcript levels varied. We conclude that a dense expression of functional Kir2.X channels underlies the more negative RPs in endothelial cells and a subset of VSMC in these arterioles, and the heterogeneous Kir function is primarily responsible for the distinct bimodal RPs among these arterioles. The fast Kir-based regenerative shifts between two RP states could form a critical mechanism for conduction/spread of vasomotion along the arteriole axis.
AB - The resting membrane potential (RP) of vascular smooth muscle cells (VSMCs) is a major determinant of cytosolic calcium concentration and vascular tone. The heterogeneity of RPs and its underlying mechanism among different vascular beds remain poorly understood. We compared the RPs and vasomotion properties between the guinea pig spiral modiolar artery (SMA), brain arterioles (BA) and mesenteric arteries (MA). We found: 1) RPs showed a robust bimodal distribution peaked at -76 and -40 mV evenly in the SMA, unevenly at -77 and -51 mV in the BA and ∼-71 and -52 mV in the MA. Ba2+ 0.1 mM eliminated their high RP peaks ∼-75 mV. 2) Cells with low RP (∼-45 mV) hyperpolarized in response to 10 mM extracellular K+, while cells with a high RP depolarized, and cells with intermediate RP (∼-58 mV) displayed an initial hyperpolarization followed by prolonged depolarization. Moderate high K+ typically induced dilation, constriction and a dilation followed by constriction in the SMA, MA and BA, respectively. 3) Boltzmann-fit analysis of the Ba2+-sensitive inward rectifier K+ (Kir) whole-cell current showed that the maximum Kir conductance density significantly differed among the vessels, and the half-activation voltage was significantly more negative in the MA. 4) Corresponding to the whole-cell data, computational modeling simulated the three RP distribution patterns and the dynamics of RP changes obtained experimentally, including the regenerative swift shifts between the two RP levels after reaching a threshold. 5) Molecular works revealed strong Kir2.1 and Kir2.2 transcripts and Kir2.1 immunolabeling in all 3 vessels, while Kir2.3 and Kir2.4 transcript levels varied. We conclude that a dense expression of functional Kir2.X channels underlies the more negative RPs in endothelial cells and a subset of VSMC in these arterioles, and the heterogeneous Kir function is primarily responsible for the distinct bimodal RPs among these arterioles. The fast Kir-based regenerative shifts between two RP states could form a critical mechanism for conduction/spread of vasomotion along the arteriole axis.
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U2 - 10.1371/journal.pone.0125266
DO - 10.1371/journal.pone.0125266
M3 - Article
C2 - 25938437
AN - SCOPUS:84929193289
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e0125266
ER -