神经血管耦合中钙信号调节机制的研究进展
摘要
<正>大脑正常的生理功能依赖于神经活动与血流动力学之间的紧密配合,这种机制称为神经血管耦合。基于该机制,与功能相关的大脑神经活动增强会引起局部脑血流量的升高。神经血管耦合由神经元、星形胶质细胞和血管构成,神经活动释放的神经递质与星形胶质细胞上的受体结合激活钙信号并传递至终足附近的血管上,激活相应信号通路并释放血管活性物质引起血管舒张。本文将对神经血管耦合中星形胶质细胞钙信号的调节机制进行综述。
引文
[1]Muoio V,Persson PB,Sendeski MM.The neurovascular unitconcept review[J].Acta Physiol(Oxf),2014,210(4):790-798.
[2]Rolfe DF,Brown GC.Cellular energy utilization and molecular origin of standard metabolic rate in mammals[J].Physiol Rev,1997,77(3):731-758.
[3]Filosa JA,Iddings JA.Astrocyte regulation of cerebral vascular tone[J].Am J Physiol Heart Circ Physiol,2013,305(5):H609-H619.
[4]Koehler RC,Gebremedhin D,Harder DR.Role of astrocytes in cerebrovascular regulation[J].J Appl Physiol(1985),2006,100(1):307-317.
[5]Straub SV,Nelson MT.Astrocytic calcium signaling:the information currency coupling neuronal activity to the cerebral microcirculation[J].Trends Cardiovasc Med,2007,17(6):183-190.
[6]Metea MR,Newman EA.Glial cells dilate and constrict blood vessels:a mechanism of neurovascular coupling[J].J Neurosci,2006,26(11):2862-2870.
[7]Girouard H,Bonev AD,Hannah RM,et al.Astrocytic endfoot Ca2+and BK channels determine both arteriolar dilation and constriction[J].Proc Natl Acad Sci U S A,2010,107(8):3811-3816.
[8]Attwell D,Buchan AM,Charpak S,et al.Glial and neuronal control of brain blood flow[J].Nature,2010,468(7321):232-243.
[9]Straub SV,Bonev AD,Wilkerson MK,et al.Dynamic inositol trisphosphate-mediated calcium signals within astrocytic endfeet underlie vasodilation of cerebral arterioles[J].J Gen Physiol,2007,128(6):659-669.
[10]Parri HR,Crunelli V.The role of Ca2+in the generation of spontaneous astrocytic Ca2+oscillations[J].Neuroscience,2003,120(4):979-992.
[11]Nilius B,Voets T.TRP channels:a TR(Ⅰ)P through a world of multifunctional cation channels[J].Pflugers Arch,2005,451(1):1-10.
[12]Dunn KM,Hill-Eubanks DC,Liedtke WB,et al.TRPV4 channels stimulate Ca2+-induced Ca2+release in astrocytic endfeet and amplify neurovascular coupling responses[J].Proc Natl Acad Sci U S A,2013,110(15):6157-6162.
[13]Orellana JA,Figueroa XF,Sánchez HA,et al.Hemichannels in the neurovascular unit and white matter under normal and inflamed conditions[J].CNS Neurol Disord Drug Targets,2011,10(3):404-414.
[14]Figueroa XF,Lillo MA,Gaete PS,et al.Diffusion of nitric oxide across cell membranes of the vascular wall requires specific connexin-based channels[J].Neuropharmacology,2013,75(12):471-478.
[15]Gaete PS,Lillo MA,Figueroa XF.Functional role of connexins and pannexins in the interaction between vascular and nervous system[J].J Cell Physiol,2014,229(10):1336-1345.
[16]de Bock M,Culot M,Wang N,et al.Connexin channels provide a target to manipulate brain endothelial calcium dynamics and blood-brain barrier permeability[J].J Cereb Blood Flow Metab,2011,31(9):1942-1957.
[17]Svenningsen P,Burford JL,Peti-Peterdi J.ATP releasing connexin 30 hemichannels mediate flow-induced calcium signaling in the collecting duct[J].Front Physiol,2013,4:292.
[18]Cherian PP,Siller-Jackson AJ,Gu S,et al.Mechanical strain opens connexin 43 hemichannels in osteocytes:a novel mechanism for the release of prostaglandin[J].Mol Biol Cell,2005,16(7):3100-3106.
[19]Suadicani SO,Iglesias R,Wang J,et al.ATP signaling is deficient in cultured Pannexin1-null mouse astrocytes[J].Glia,2012,60(7):1106-1116.
[20]Meno JR,Crum AV,Winn HR.Effect of adenosine receptor blockade on pial arteriolar dilation during sciatic nerve stimulation[J].Am J Physiol Heart Circ Physiol,2001,281(5):H2018-H2027.
[21]Tsutsui M,Ueno S,Toyohira Y,et al.Structure and function of nitric oxide synthases[J].Tanpakushitsu Kakusan Koso,2002,47(15):2024-2031.
[22]BroíckováC,Otáhal J.Effect of an inhibitor of neuronal nitric oxide synthase 7-nitroindazole on cerebral hemodynamic response and brain excitability in urethane-anesthetized rats[J].Physiol Res,2013,62 Suppl 1:S57-S66.
[23]Martínez Rruiz A,Araújo IM,Izguierdo-álvarez A,et al.Specificity in S-nitrosylation:a short-range mechanism for NO signaling?[J].Antioxid Redox Signal,2013,19(11):1220-1235.
[24]Retamal MA,Cortés CJ,Luis R,et al.S-nitrosylation and permeation through connexin 43 hemichannels in astrocytes:induction by oxidant stress and reversal by reducing agents[J].Proc Natl Acad Sci U S A,2006,103(12):4475-4480.
[25]Li N,Sul JY,Haydon PG.A calcium-induced calcium influx factor,nitric oxide,modulates the refilling of calcium stores in astrocytes[J].J Neurosci,2003,23(32):10302-10310.
[26]Stobart JL,Lu L,Anderson HD,et al.Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide synthase[J].Proc Natl Acad Sci U S A,2013,110(8):3149-3154.
[2]Rolfe DF,Brown GC.Cellular energy utilization and molecular origin of standard metabolic rate in mammals[J].Physiol Rev,1997,77(3):731-758.
[3]Filosa JA,Iddings JA.Astrocyte regulation of cerebral vascular tone[J].Am J Physiol Heart Circ Physiol,2013,305(5):H609-H619.
[4]Koehler RC,Gebremedhin D,Harder DR.Role of astrocytes in cerebrovascular regulation[J].J Appl Physiol(1985),2006,100(1):307-317.
[5]Straub SV,Nelson MT.Astrocytic calcium signaling:the information currency coupling neuronal activity to the cerebral microcirculation[J].Trends Cardiovasc Med,2007,17(6):183-190.
[6]Metea MR,Newman EA.Glial cells dilate and constrict blood vessels:a mechanism of neurovascular coupling[J].J Neurosci,2006,26(11):2862-2870.
[7]Girouard H,Bonev AD,Hannah RM,et al.Astrocytic endfoot Ca2+and BK channels determine both arteriolar dilation and constriction[J].Proc Natl Acad Sci U S A,2010,107(8):3811-3816.
[8]Attwell D,Buchan AM,Charpak S,et al.Glial and neuronal control of brain blood flow[J].Nature,2010,468(7321):232-243.
[9]Straub SV,Bonev AD,Wilkerson MK,et al.Dynamic inositol trisphosphate-mediated calcium signals within astrocytic endfeet underlie vasodilation of cerebral arterioles[J].J Gen Physiol,2007,128(6):659-669.
[10]Parri HR,Crunelli V.The role of Ca2+in the generation of spontaneous astrocytic Ca2+oscillations[J].Neuroscience,2003,120(4):979-992.
[11]Nilius B,Voets T.TRP channels:a TR(Ⅰ)P through a world of multifunctional cation channels[J].Pflugers Arch,2005,451(1):1-10.
[12]Dunn KM,Hill-Eubanks DC,Liedtke WB,et al.TRPV4 channels stimulate Ca2+-induced Ca2+release in astrocytic endfeet and amplify neurovascular coupling responses[J].Proc Natl Acad Sci U S A,2013,110(15):6157-6162.
[13]Orellana JA,Figueroa XF,Sánchez HA,et al.Hemichannels in the neurovascular unit and white matter under normal and inflamed conditions[J].CNS Neurol Disord Drug Targets,2011,10(3):404-414.
[14]Figueroa XF,Lillo MA,Gaete PS,et al.Diffusion of nitric oxide across cell membranes of the vascular wall requires specific connexin-based channels[J].Neuropharmacology,2013,75(12):471-478.
[15]Gaete PS,Lillo MA,Figueroa XF.Functional role of connexins and pannexins in the interaction between vascular and nervous system[J].J Cell Physiol,2014,229(10):1336-1345.
[16]de Bock M,Culot M,Wang N,et al.Connexin channels provide a target to manipulate brain endothelial calcium dynamics and blood-brain barrier permeability[J].J Cereb Blood Flow Metab,2011,31(9):1942-1957.
[17]Svenningsen P,Burford JL,Peti-Peterdi J.ATP releasing connexin 30 hemichannels mediate flow-induced calcium signaling in the collecting duct[J].Front Physiol,2013,4:292.
[18]Cherian PP,Siller-Jackson AJ,Gu S,et al.Mechanical strain opens connexin 43 hemichannels in osteocytes:a novel mechanism for the release of prostaglandin[J].Mol Biol Cell,2005,16(7):3100-3106.
[19]Suadicani SO,Iglesias R,Wang J,et al.ATP signaling is deficient in cultured Pannexin1-null mouse astrocytes[J].Glia,2012,60(7):1106-1116.
[20]Meno JR,Crum AV,Winn HR.Effect of adenosine receptor blockade on pial arteriolar dilation during sciatic nerve stimulation[J].Am J Physiol Heart Circ Physiol,2001,281(5):H2018-H2027.
[21]Tsutsui M,Ueno S,Toyohira Y,et al.Structure and function of nitric oxide synthases[J].Tanpakushitsu Kakusan Koso,2002,47(15):2024-2031.
[22]BroíckováC,Otáhal J.Effect of an inhibitor of neuronal nitric oxide synthase 7-nitroindazole on cerebral hemodynamic response and brain excitability in urethane-anesthetized rats[J].Physiol Res,2013,62 Suppl 1:S57-S66.
[23]Martínez Rruiz A,Araújo IM,Izguierdo-álvarez A,et al.Specificity in S-nitrosylation:a short-range mechanism for NO signaling?[J].Antioxid Redox Signal,2013,19(11):1220-1235.
[24]Retamal MA,Cortés CJ,Luis R,et al.S-nitrosylation and permeation through connexin 43 hemichannels in astrocytes:induction by oxidant stress and reversal by reducing agents[J].Proc Natl Acad Sci U S A,2006,103(12):4475-4480.
[25]Li N,Sul JY,Haydon PG.A calcium-induced calcium influx factor,nitric oxide,modulates the refilling of calcium stores in astrocytes[J].J Neurosci,2003,23(32):10302-10310.
[26]Stobart JL,Lu L,Anderson HD,et al.Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide synthase[J].Proc Natl Acad Sci U S A,2013,110(8):3149-3154.