The role of ion channels on the physiology of the neurovascular unit and the regulation of cerebral blood flow

Year 2021, Volume: 13 Issue: 2, 1004 - 1013, 11.02.2022

Marcelıno Montiel-herrera , Denisse García-villa Guillermo López-cervantes Daniel Reyes-haro J. Abraham Domínguez-avila Gustavo A. González-aguilar

https://doi.org/10.37212/jcnos.1054986

Cited By: 1

Abstract

The neurovascular unit, composed of neurons, brain endothelial cells, pericytes, microglia, and astrocytes, regulates cerebral blood flow. The physical and chemical signals govern the physiology of the neurovascular unit within the network composed of its cellular components. Astrocytes have an essential role in this network since they have a privileged anatomical relationship with the rest of the cells. They are capable of sensing signals released by their neighboring cells, releasing chemical transmitters, and controlling the extracellular K+ concentration. Moreover, astrocytes play a crucial role in providing oxygen and nutrients to neurons during high neuronal firing activity. This manuscript will briefly discuss the recent evidence of astrocytes' contribution and their plethora of ion channels to the leading cellular mechanisms involved in the physiology of the neurovascular unit.

Keywords

ion channels , astrocyte end-feet , neurovascular , endothelial cell , vascular smooth muscle cell , capillaries.

Supporting Institution

SEP-PRODEP

Project Number

511-6/17-7715

References

• Abbott NJ, Pizzo ME, Preston JE, et al (2018) The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system? Acta Neuropathol (Berl) 135, 387–407.
• Alexander SP, Striessnig J, Kelly E, et al (2017) The concise guide to pharmacology 2017/18: Voltage‐gated ion channels. Br J Pharmacol 174, S160–S194.
• Byron KL, Brueggemann LI (2018) Kv7 potassium channels as signal transduction intermediates in the control of microvascular tone. Microcirc 25, 1-113.
• Cho C-H, Hwang EM, Park J-Y (2017) Emerging Roles of TWIK-1 Heterodimerization in the Brain. Int J Mol Sci 19, 51.
• Covelo A, Araque A (2018) Neuronal activity determines distinct gliotransmitter release from a single astrocyte. eLife 7, e32237.
• Evanko DS, Zhang Q, Zorec R, Haydon PG (2004) Defining pathways of loss and secretion of chemical messengers from astrocytes. Glia 47, 233–240.
• Filosa JA (2015) The neurovascular unit and the role of astrocytes in the regulation of vascular tone. Colloquium series on neuroglia in biology and medicine: from physiology to disease 2, 1-60.
• Girouard H, Bonev AD, Hannah RM, et al (2010) Astrocytic endfoot Ca2+ and BK channels determine both arteriolar dilation and constriction. Proc Natl Acad Sci 107, 3811–3816.
• Gollasch M, Welsh DG, Schubert R (2018) Perivascular adipose tissue and the dynamic regulation of Kv7 and Kir channels: Implications for resistant hypertension. Microcirc 25, e12434.
• Gordon GRJ, Choi HB, Rungta RL, et al (2008) Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456, 745–749.
• Goto K, Ohtsubo T, Kitazono T (2018) Endothelium-Dependent Hyperpolarization (EDH) in Hypertension: The Role of Endothelial Ion Channels. Int J Mol Sci 19, 315.
• Hall CN, Reynell C, Gesslein B, et al (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508, 55–60.
• Harraz OF, Longden TA, Hill-Eubanks D, Nelson MT (2018) PIP2 depletion promotes TRPV4 channel activity in mouse brain capillary endothelial cells. eLife 7:e38689.
• Hasan R, Jaggar JH (2018) KV channel trafficking and control of vascular tone. Microcirc 25, e12418.
• Hashitani H, Lang RJ (2016) Spontaneous activity in the microvasculature of visceral organs: role of pericytes and voltage‐dependent Ca2+ channels. J Physiol 594, 555–565.
• Hwang EM, Kim E, Yarishkin O, et al (2014) A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes. Nat Commun 5:3227.
• Hill RA, Tong L, Yuan P, et al (2015) Regional Blood Flow in the Normal and Ischemic Brain Is Controlled by Arteriolar Smooth Muscle Cell Contractility and Not by Capillary Pericytes. Neuron 87, 95–110.
• Hille B (2011) Ion channels of excitable membrane 3rd ed. Sunderland (MA): Sinauer Associates, Inc; 134-156. Jackson WF (2005) Potassium Channels in the Peripheral Microcirculation. Microcirc 12, 113–127.
• Kur J, Newman EA (2014) Purinergic control of vascular tone in the retina. J Pgysyiol 592, 491-504.
• Longden TA, Hill-Eubanks DC, Nelson MT (2016) Ion channel networks in the control of cerebral blood flow. J Cereb Blood Flow Metab 36, 492–512.
• Masamoto K, Unekawa M, Watanabe T, et al (2015) Unveiling astrocytic control of cerebral blood flow with optogenitics. Scientific Reports 5:11455.
• McConnell HL, Kersh CN, Woltjer RL, et al (2017) The translational significance of the neurovascular unit. J Biol Chem 292, 762-770.
• Milton M, Smith PD (2018) It’s All about Timing: The Involvement of Kir4.1 Channel Regulation in Acute Ischemic Stroke Pathology. Front Cell Neurosci 12, 36.
• Mishra A (2017) Binaural blood flow control by astrocytes: listening to synapses and the vasculature. J Physiol 595, 1885-1902.
• Mishra A, Reynolds JP, Chen Y, et al (2016) Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles. Nat Neurosci 19, 1619–1627.
• Montiel-Herrera M, García-Colunga J (2010) Current profiles of astrocytes from the corpus callosum of newborn and 28-day-old rats. Neurosci Lett 485, 189–193.
• Orellana JA (2016) Physiological Functions of Glial Cell Hemichannels. In: Glial Cells in Health and Disease of the CNS. Springer, Cham, pp 93–108.
• Otsu Y, Couchman K, Lyons DG, et al (2015) Calcium dynamics in astrocyte processes during neurovascular coupling. Nat Neurosci 18, 210–218.
• Puro DG (2007) Physiology and Pathobiology of the Pericyte-Containing Retinal Microvasculature: New Developments. Microcirculation 14, 1–10.
• Reeson P, Choi K, Brown CE (2018) VEGF signaling regulates the fate of obstructed capillaries in mouse cortex. eLife 7, e33670.
• Reyes-Haro D, Miledi R, García-Colunga J (2005) Potassium currents in primary cultured astrocytes from the rat corpus callosum. J Neurocytol 34, 411-420.
• Rosenegger DG, Tran CHT, Cusulim JIW, et al (2015) Tonic Local Brain Blood flow control by astrocytes independent of phasic neurovascular coupling. J Neurosci 35, 13463-13474.
• Rungta RL, Osmanski BF, Boido D, Tanter M & Charpak S (2017) Ligth controls cerebral blow flow in naïve animals. Nature communications 8:14191.
• Seifert G, Henneberger C, Steinhäuser C (2018) Diversity of astrocyte potassium channels: An update. Brain Res Bull 136, 26–36.
• Sibille J, Duc KD, Holcman D, Rouach N (2015) The Neuroglial Potassium Cycle during Neurotransmission: Role of Kir4.1 Channels. PLOS Comput Biol 11, e1004137.
• Stobart JL, Ferrari KD, Barrett MJP, et al (2018) Cortical Circuit Activity Evokes Rapid Astrocyte Calcium Signals on a Similar Timescale to Neurons. Neuron 98, 726-735.
• Sugiyama T (2014) Role of P2X7 receptors in the development of diabetic retinopathy. World J Diabetes 5, 141–145.
• Vivas O, Moreno CM, Santana LF, Hille B (2017) Proximal clustering between BK and CaV1.3 channels promotes functional coupling and BK channel activation at low voltage. eLife 6, e28029.
• Wolburg H, Noell S, Wolburg-Buchholz K, et al (2009) Agrin, Aquaporin-4, and Astrocyte Polarity as an Important Feature of the Blood-Brain Barrier. The Neuroscientist 15, 180–193.
• Woo DH, Han K-S, Shim JW, et al (2012) TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR Activation. Cell 151, 25–40.
• Zhang Xiao, Wan Jie‐Qing, Tong Xiao‐Ping (2018) Potassium channel dysfunction in neurons and astrocytes in Huntington’s disease. CNS Neurosci Ther 24, 311–318.
• Zhang Y, Chen K, Sloan SA, et al (2014) An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex. J Neurosci 34, 11929–11947.
• Zhu Y, Ye P, Chen S, Zhang D-M (2018) Functional regulation of large conductance Ca2+-activated K+ channels in vascular diseases. Metabolism 83, 75–80.