scholarly journals Abnormal neurovascular coupling as a cause of excess cerebral vasodilation in familial migraine

2019 ◽  
Vol 116 (12) ◽  
pp. 2009-2020
Author(s):  
Christian Staehr ◽  
Rajkumar Rajanathan ◽  
Dmitry D Postnov ◽  
Lise Hangaard ◽  
Elena V Bouzinova ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Migraine Attack ◽  
Brain Slices ◽  
Neurovascular Coupling ◽  
Laser Speckle ◽  
Muscle Membrane ◽  
Neuronal Excitation ◽  
Channel Expression ◽  
Hyperaemic Response ◽  
Kir2.1 Channel

Abstract Aims Acute migraine attack in familial hemiplegic migraine type 2 (FHM2) patients is characterized by sequential hypo- and hyperperfusion. FHM2 is associated with mutations in the Na, K-ATPase α2 isoform. Heterozygous mice bearing one of these mutations (α2+/G301R mice) were shown to have elevated cerebrovascular tone and, thus, hypoperfusion that might lead to elevated concentrations of local metabolites. We hypothesize that these α2+/G301R mice also have increased cerebrovascular hyperaemic responses to these local metabolites leading to hyperperfusion in the affected part of the brain. Methods and results Neurovascular coupling was compared in α2+/G301R and matching wild-type (WT) mice using Laser Speckle Contrast Imaging. In brain slices, parenchymal arteriole diameter and intracellular calcium changes in neuronal tissue, astrocytic endfeet, and smooth muscle cells in response to neuronal excitation were assessed. Wall tension and smooth muscle membrane potential were measured in isolated middle cerebral arteries. Quantitative polymerase chain reaction, western blot, and immunohistochemistry were used to assess the molecular background underlying the functional changes. Whisker stimulation induced larger increase in blood perfusion, i.e. hyperaemic response, of the somatosensory cortex of α2+/G301R than WT mice. Neuronal excitation was associated with larger parenchymal arteriole dilation in brain slices from α2+/G301R than WT mice. These hyperaemic responses in vivo and ex vivo were inhibited by BaCl2, suggesting involvement of inward-rectifying K+ channels (Kir). Relaxation to elevated bath K+ was larger in arteries from α2+/G301R compared to WT mice. This difference was endothelium-dependent. Endothelial Kir2.1 channel expression was higher in arteries from α2+/G301R mice. No sex difference in functional responses and Kir2.1 expression was found. Conclusion This study suggests that an abnormally high cerebrovascular hyperaemic response in α2+/G301R mice is a result of increased endothelial Kir2.1 channel expression. This may be initiated by vasospasm-induced accumulation of local metabolites and underlie the hyperperfusion seen in FHM2 patients during migraine attack.

scholarly journals Enhanced Parenchymal Arteriole Tone and Astrocyte Signaling Protect Neurovascular Coupling Mediated Parenchymal Arteriole Vasodilation in the Spontaneously Hypertensive Rat

2015 ◽  
Vol 35 (7) ◽  
pp. 1127-1136 ◽  
Author(s):  
Jennifer A Iddings ◽  
Ki Jung Kim ◽  
Yiqiang Zhou ◽  
Haruki Higashimori ◽  
Jessica A Filosa
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Metabotropic Glutamate Receptor ◽  
Brain Slices ◽  
Neurovascular Coupling ◽  
Receptor Activation ◽  
Spontaneously Hypertensive

Functional hyperemia is the regional increase in cerebral blood flow upon increases in neuronal activity which ensures that the metabolic demands of the neurons are met. Hypertension is known to impair the hyperemic response; however, the neurovascular coupling mechanisms by which this cerebrovascular dysfunction occurs have yet to be fully elucidated. To determine whether altered cortical parenchymal arteriole function or astrocyte signaling contribute to blunted neurovascular coupling in hypertension, we measured parenchymal arteriole reactivity and vascular smooth muscle cell Ca2+ dynamics in cortical brain slices from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. We found that vasoconstriction in response to the thromboxane A2 receptor agonist U46619 and basal vascular smooth muscle cell Ca2+ oscillation frequency were significantly increased in parenchymal arterioles from SHR. In perfused and pressurized parenchymal arterioles, myogenic tone was significantly increased in SHR. Although K+-induced parenchymal arteriole dilations were similar in WKY and SHR, metabotropic glutamate receptor activation-induced parenchymal arteriole dilations were enhanced in SHR. Further, neuronal stimulation-evoked parenchymal arteriole dilations were similar in SHR and WKY. Our data indicate that neurovascular coupling is not impaired in SHR, at least at the level of the parenchymal arterioles.

Reduced molecular expression of K+ channel proteins in vascular smooth muscle from rats made hypertensive with Nω-nitro-l-arginine

2005 ◽  
Vol 289 (3) ◽  
pp. H1277-H1283 ◽  
Author(s):  
Ian N. Bratz ◽  
Gregory M. Dick ◽  
L. Donald Partridge ◽  
Nancy L. Kanagy
Keyword(s):  
Smooth Muscle ◽  
Companion Paper ◽  
Muscle Membrane ◽  
K Channel ◽  
Channel Blockers ◽  
Western Blots ◽  
Channel Function ◽  
Voltage Dependent ◽  
Channel Expression ◽  
Smooth Muscle Membrane

Smooth muscle membrane potential ( Em) depends on K+ channels, and arteries from rats made hypertensive with Nω-nitro-l-arginine (LHR) are depolarized compared with control. We hypothesized that decreased K+ channel function, due to decreased K+ channel protein expression, underlies Em depolarization. Furthermore, K+ channel blockers should move control Em (−46 ± 1 mV) toward that in LHR (−37 ± 2 mV) and normalize contraction. The Em vs. K+ relationship was less steep in LHR (23 ± 2 vs. 28 ± 1 mV/log K+ concentration), and contractile sensitivity to K+ was increased (EC50 = 37 ± 1 vs. 23 ± 1 mM). Iberiotoxin (10 nM), an inhibitor of large-conductance Ca2+-activated K+ (BKCa) channels, depolarized control and LHR Em to −35 ± 1 and −30 ± 2 mV, respectively; however, effects on K+ sensitivity were more profound in LHR (EC50 = 25 ± 2 vs. 15 ± 3 mM). The voltage-dependent K+ (KV) channel blocker 4-aminopyridine (3 mM) depolarized control Em to the level of LHR (−28 ± 1 vs. −28 ± 1 mV); however, effects on K+ sensitivity were greater in LHR (EC50 = 17 ± 4 vs. 4 ± 4 mM). Western blots revealed reduced BKCa and KV1.5 channel expression in LHR arteries. The findings suggest that diminished expression of K+ channels contributes to depolarization and enhanced contractile sensitivity. These conclusions are supported by direct electrophysiological assessment of BKCa and KV channel function in control and LHR smooth muscle cells [see companion paper (Bratz IN, Swafford AN Jr, Kanagy NL, and Dick GM. Am J Physiol Heart Circ Physiol 289: H1284–H1290, 2005)].

scholarly journals Remodeling of Arterial Tone Regulation in Postnatal Development: Focus on Smooth Muscle Cell Potassium Channels

2021 ◽  
Vol 22 (11) ◽  
pp. 5413
Author(s):  
Anastasia A. Shvetsova ◽  
Dina K. Gaynullina ◽  
Olga S. Tarasova ◽  
Rudolf Schubert
Keyword(s):  
Smooth Muscle ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Postnatal Development ◽  
Sympathetic Innervation ◽  
Treatment Strategies ◽  
Muscle Membrane ◽  
Postnatal Life ◽  
Vascular Control ◽  
Bkca Channels

Maturation of the cardiovascular system is associated with crucial structural and functional remodeling. Thickening of the arterial wall, maturation of the sympathetic innervation, and switching of the mechanisms of arterial contraction from calcium-independent to calcium-dependent occur during postnatal development. All these processes promote an almost doubling of blood pressure from the moment of birth to reaching adulthood. This review focuses on the developmental alterations of potassium channels functioning as key smooth muscle membrane potential determinants and, consequently, vascular tone regulators. We present evidence that the pattern of potassium channel contribution to vascular control changes from Kir2, Kv1, Kv7 and TASK-1 channels to BKCa channels with maturation. The differences in the contribution of potassium channels to vasomotor tone at different stages of postnatal life should be considered in treatment strategies of cardiovascular diseases associated with potassium channel malfunction.

scholarly journals Neurovascular coupling during optogenetic functional activation: Local and remote stimulus-response characteristics, and uncoupling by spreading depression

2019 ◽  
Vol 40 (4) ◽  
pp. 808-822 ◽  
Author(s):  
Maximilian Böhm ◽  
David Y Chung ◽  
Carlos A Gómez ◽  
Tao Qin ◽  
Tsubasa Takizawa ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Spreading Depression ◽  
Barrel Cortex ◽  
Disease Process ◽  
Neurovascular Coupling ◽  
Laser Speckle ◽  
Cortical Activation ◽  
Somatosensory Stimulation ◽  
Response Characteristics ◽  
Electrophysiological Activity

Neurovascular coupling is a fundamental response that links activity to perfusion. Traditional paradigms of neurovascular coupling utilize somatosensory stimulation to activate the primary sensory cortex through subcortical relays. Therefore, examination of neurovascular coupling in disease models can be confounded if the disease process affects these multisynaptic pathways. Optogenetic stimulation is an alternative to directly activate neurons, bypassing the subcortical relays. We employed minimally invasive optogenetic cortical activation through intact skull in Thy1-channelrhodopsin-2 transgenic mice, examined the blood flow changes using laser speckle imaging, and related these to evoked electrophysiological activity. Our data show that optogenetic activation of barrel cortex triggers intensity- and frequency-dependent hyperemia both locally within the barrel cortex (>50% CBF increase), and remotely within the ipsilateral motor cortex (>30% CBF increase). Intriguingly, activation of the barrel cortex causes a small (∼10%) but reproducible hypoperfusion within the contralateral barrel cortex, electrophysiologically linked to transhemispheric inhibition. Cortical spreading depression, known to cause neurovascular uncoupling, diminishes optogenetic hyperemia by more than 50% for up to an hour despite rapid recovery of evoked electrophysiological activity, recapitulating a unique feature of physiological neurovascular coupling. Altogether, these data establish a minimally invasive paradigm to investigate neurovascular coupling for longitudinal characterization of cerebrovascular pathologies.

L-type Ca2+ channel expression along feline smooth muscle oesophagus

2004 ◽  
Vol 16 (3) ◽  
pp. 325-334 ◽  
Author(s):  
A. Muinuddin ◽  
J. Ji ◽  
L. Sheu ◽  
Y. Kang ◽  
H. Y. Gaisano ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Channel Expression

scholarly journals Glutamate regulates Ca2+ signals in smooth muscle cells of newborn piglet brain slice arterioles through astrocyte- and heme oxygenase-dependent mechanisms

2010 ◽  
Vol 298 (2) ◽  
pp. H562-H569 ◽  
Author(s):  
Qi Xi ◽  
Edward Umstot ◽  
Guiling Zhao ◽  
Damodaran Narayanan ◽  
Charles W. Leffler ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Heme Oxygenase ◽  
Guanylyl Cyclase ◽  
Brain Slices ◽  
Soluble Guanylyl Cyclase ◽  
Muscle Cells ◽  
Newborn Piglet ◽  
Signal Modulation ◽  
Cerebral Arterioles

Glutamate is the principal cerebral excitatory neurotransmitter and dilates cerebral arterioles to match blood flow to neural activity. Arterial contractility is regulated by local and global Ca2+ signals that occur in smooth muscle cells, but modulation of these signals by glutamate is poorly understood. Here, using high-speed confocal imaging, we measured the Ca2+ signals that occur in arteriole smooth muscle cells of newborn piglet tangential brain slices, studied signal regulation by glutamate, and investigated the physiological function of heme oxygenase (HO) and carbon monoxide (CO) in these responses. Glutamate elevated Ca2+ spark frequency by ∼188% and reduced global intracellular Ca2+ concentration ([Ca2+]i) to ∼76% of control but did not alter Ca2+ wave frequency in brain arteriole smooth muscle cells. Isolation of cerebral arterioles from brain slices abolished glutamate-induced Ca2+ signal modulation. In slices treated with l-2-α-aminoadipic acid, a glial toxin, glutamate did not alter Ca2+ sparks or global [Ca2+]i but did activate Ca2+ waves. This shift in Ca2+ signal modulation by glutamate did not occur in slices treated with d-2-α-aminoadipic acid, an inactive isomer of l-2-α-aminoadipic acid. In the presence of chromium mesoporphyrin, a HO blocker, glutamate inhibited Ca2+ sparks and Ca2+ waves and did not alter global [Ca2+]i. In isolated arterioles, CORM-3 [tricarbonylchloro(glycinato)ruthenium(II)], a CO donor, activated Ca2+ sparks and reduced global [Ca2+]i. These effects were blocked by 1 H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one, a soluble guanylyl cyclase inhibitor. Collectively, these data indicate that glutamate can modulate Ca2+ sparks, Ca2+ waves, and global [Ca2+]i in arteriole smooth muscle cells via mechanisms that require astrocytes and HO. These data also indicate that soluble guanylyl cyclase is involved in CO activation of Ca2+ sparks in arteriole smooth muscle cells.

L‐type calcium channel expression depends on the differentiated state of vascular smooth muscle cells

1998 ◽  
Vol 12 (7) ◽  
pp. 593-601 ◽  
Author(s):  
Maik Gollasch ◽  
Hannelore Haase ◽  
Christian Ried ◽  
Carsten Lindschau ◽  
Ingo Morano ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Calcium Channel ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Channel Expression

Endothelium-dependent hyperpolarization elicited by adenine compounds in rabbit carotid artery

1991 ◽  
Vol 260 (4) ◽  
pp. H1037-H1042 ◽  
Author(s):  
G. Chen ◽  
H. Suzuki
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Direct Action ◽  
Smooth Muscles ◽  
Muscle Membrane ◽  
Dependent Manner ◽  
Rabbit Carotid Artery ◽  
Mechanical Removal ◽  
Smooth Muscle Membrane ◽  
Adventitial Cells

Electrical responses of the membrane of intimal and adventitial smooth muscle cells of the rabbit carotid artery to ATP, ADP, AMP, and adenosine were recorded. In intimal cells, these compounds hyperpolarized the membrane. Mechanical removal of the endothelium altered the responses to ATP and ADP to one of a transient depolarization, with no alteration of the response to AMP and adenosine. In the adventitial cells, ATP and ADP produced a transient depolarization, whereas AMP and adenosine produced a sustained hyperpolarization, irrespective of the presence or absence of the endothelium. In tissues with an intact endothelium, 5'-adenylylimidodiphosphate tetralithium salt and alpha,beta-methylene ATP (mATP) transiently depolarized the membrane in these smooth muscles. In case of stabilization with mATP, only hyperpolarization was generated by ATP, in an endothelium-dependent manner. Our interpretation of these observations is that 1) ATP and ADP depolarize smooth muscle membrane by a direct action and hyperpolarize the membrane indirectly through the release of endothelium-derived hyperpolarizing factor, 2) AMP and adenosine hyperpolarize the membrane, independently of the endothelium, and 3) ATP receptors present on the endothelial cell membrane differ from those on smooth muscle membrane.

Diversity of neurogenic smooth muscle electrical rhythmicity in mouse proximal colon

2020 ◽  
Vol 318 (2) ◽  
pp. G244-G253 ◽  
Author(s):  
Nick J. Spencer ◽  
Lee Travis ◽  
Lukasz Wiklendt ◽  
Timothy J. Hibberd ◽  
Marcello Costa ◽  
...  
Keyword(s):  
Nervous System ◽  
Smooth Muscle ◽  
Enteric Nervous System ◽  
Extracellular Recording ◽  
Proximal Colon ◽  
Proximal Region ◽  
Muscle Membrane ◽  
Mouse Colon ◽  
Cross Correlation Analysis

The mechanisms underlying electrical rhythmicity in smooth muscle of the proximal colon are incompletely understood. Our aim was to identify patterns of electrical rhythmicity in smooth muscle of the proximal region of isolated whole mouse colon and characterize their mechanisms of origin. Two independent extracellular recording electrodes were used to record the patterns of electrical activity in smooth muscle of the proximal region of whole isolated mouse colon. Cross-correlation analysis was used to quantify spatial coordination of these electrical activities over increasing electrode separation distances. Four distinct neurogenic patterns of electrical rhythmicity were identified in smooth muscle of the proximal colon, three of which have not been identified and consisted of bursts of rhythmic action potentials at 1–2 Hz that were abolished by hexamethonium. These neurogenic patterns of electrical rhythmicity in smooth muscle were spatially and temporally synchronized over large separation distances (≥2 mm rosto-caudal axis). Myogenic slow waves could be recorded from the same preparations, but they showed poor spatial and temporal coordination over even short distances (≤1 mm rostro-caudal axis). It is not commonly thought that electrical rhythmicity in gastrointestinal smooth muscle is dependent upon the enteric nervous system. Here, we identified neurogenic patterns of electrical rhythmicity in smooth muscle of the proximal region of isolated mouse colon, which are dependent on synaptic transmission in the enteric nervous system. If the whole colon is studied in vitro, recordings can preserve novel neurogenic patterns of electrical rhythmicity in smooth muscle. NEW & NOTEWORTHY Previously, it has not often been thought that electrical rhythmicity in smooth muscle of the gastrointestinal tract is dependent upon the enteric nervous system. We identified patterns of electrical rhythmicity in smooth muscle of the mouse proximal colon that were abolished by hexamethonium and involved the temporal synchronization of smooth muscle membrane potential over large spatial fields. We reveal different patterns of electrical rhythmicity in colonic smooth muscle that are dependent on the ENS.

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