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

In the rodent cerebral circulation, inward rectifying K+ (KIR) channels set resting tone and the distance over which electrical phenomena spread along the arterial wall. The present study sought to translate these observations into human cerebral arteries obtained from resected brain tissue. Computational modeling and a conduction assay first defined the impact of KIR channels on electrical communication; patch-clamp electrophysiology, quantitative PCR, and immunohistochemistry then characterized KIR2.x channel expression/activity. In keeping with rodent observations, computer modeling highlighted that KIR blockade should constrict cerebral arteries and attenuate electrical communication if functionally expressed. Surprisingly, Ba2+ (a KIR channel inhibitor) had no effect on human cerebral arterial tone or intercellular conduction. In alignment with these observations, immunohistochemistry and patch-clamp electrophysiology revealed minimal KIR channel expression/activity in both smooth muscle and endothelial cells. This absence may be reflective of chronic stress as dysphormic neurons, leukocyte infiltrate, and glial fibrillary acidic protein expression was notable in the epileptic cortex. In closing, KIR2.x channel expression is limited in human cerebral arteries from patients with epilepsy and thus has little impact on resting tone or the spread of vasomotor responses. NEW & NOTEWORTHY KIR2.x channels are expressed in rodent cerebral arterial smooth muscle and endothelial cells. As they are critical to setting membrane potential and the distance signals conduct, we sought to translate this work into humans. Surprisingly, KIR2.x channel activity/expression was limited in human cerebral arteries, a paucity tied to chronic brain stress in the epileptic cortex. Without substantive expression, KIR2.x channels were unable to govern arterial tone or conduction.

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Hypothyroidism does not affect the dihydropyridine sensitivity of precontracted murine uterus

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y03-090 ◽

2003 ◽

Vol 81 (9) ◽

pp. 890-893 ◽

Cited By ~ 3

Author(s):

Jörg W Wegener ◽

Matthias Lee ◽

Franz Hofmann

Keyword(s):

Smooth Muscle ◽

Cell Differentiation ◽

Thyroid Hormone ◽

Thyroid Hormones ◽

Rat Uterus ◽

Hormone Levels ◽

Uterine Muscle ◽

Channel Expression ◽

Thyroid Hormone Levels ◽

Pregnant State

Thyroid hormones are known to influence various processes of cell differentiation. Recently, it was reported that hypothyroidism reduces the sensitivity to Ca2+-channel antagonists in the rat uterus. We examined the sensitivity to dihydropyridines of the uterus from mice that had reduced thyroid hormone levels. Isradipine relaxed with the same potency precontracted uterine muscle strips from control and hypothyroid mice, independently from a pseudo-pregnant state. These results demonstrate that hypothyroidism does not change dihydropyridine sensitivity (i.e., the pattern of Ca2+-channel expression) in the murine uterus.Key words: uterus, smooth muscle, Ca2+ channel, isradipine.

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Mibefradil suppresses the proliferation of pulmonary artery smooth muscle cells

Journal of Investigative Medicine ◽

10.1136/jim-d-15-00167 ◽

2016 ◽

Vol 64 (1) ◽

pp. 45-49 ◽

Cited By ~ 1

Author(s):

Hong-Hong Li ◽

Li-Jian Xie ◽

Ting-Ting Xiao ◽

Min Huang ◽

Jie Shen

Keyword(s):

Smooth Muscle ◽

Pulmonary Artery ◽

Transient Receptor Potential ◽

Critical Role ◽

Receptor Potential ◽

Channel Expression ◽

Intracellular Ca ◽

Pulmonary Arterial ◽

Pulmonary Artery Smooth Muscle ◽

Transient Receptor

Intracellular Ca2+ levels play a critical role in the regulation of vasodilation and vasoconstriction by stimulating pulmonary artery smooth muscle cell (PASMC) proliferation, which is important in the pathogenesis of pulmonary arterial hypertension (PAH); however, L-type Ca2+ channel antagonists are useful in only few patients with PAH. The present study sought to assess the effect of mibefradil, which blocks T-type Ca2+ channels, on PASMC proliferation and Ca2+ channel profile. Human PASMCs were stimulated with 25 ng/mL platelet-derived growth factor-BB (PDGF-BB) with and without 10 µM mibefradil or 100 nM sildenafil. After 48 or 72 h, PASMC proliferation and Ca2+ channel expression were assessed by MTT assays and western blot analysis, respectively. PDGF-BB-induced PASMC proliferation at 72 h (p<0.01), which was inhibited by both sildenafil and mibefradil (p<0.01). Transient receptor potential Ca2+ channel 6 (TRPC6) expression was significantly increased with PDGF-BB stimulation (p=0.009); however, no changes in TRPC1, TRPC3, CAV1.2, and CAV3.2 levels were observed. Although both TRPC1 and CAV1.2 expression levels were increased in PDGF-stimulated PASMCs on mibefradil and sildenafil treatment, it was not statistically significant (p=0.086 and 1.000, respectively). Mibefradil inhibits PDGF-BB-stimulated PASMC proliferation; however, the mechanism through which it functions remains to be determined. Further studies are required to elucidate the full therapeutic value of mibefradil for PAH.

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Endogenous testosterone increases L-type Ca2+ channel expression in porcine coronary smooth muscle

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00258.2004 ◽

2004 ◽

Vol 287 (5) ◽

pp. H2091-H2098 ◽

Cited By ~ 36

Author(s):

D. K. Bowles ◽

K. K. Maddali ◽

V. K. Ganjam ◽

L. J. Rubin ◽

D. L. Tharp ◽

...

Keyword(s):

Smooth Muscle ◽

Coronary Arteries ◽

Serum Testosterone ◽

Coronary Smooth Muscle ◽

Voltage Gated ◽

Androgen Receptor Antagonist ◽

Hormone Response Element ◽

Channel Expression ◽

Expression And Activity

Evidence indicates that gender and sex hormonal status influence cardiovascular physiology and pathophysiology. We recently demonstrated increased L-type voltage-gated Ca2+ current ( ICa,L) in coronary arterial smooth muscle (CASM) of male compared with female swine. The promoter region of the L-type voltage-gated Ca2+ channel (VGCC) (Cav1.2) gene contains a hormone response element that is activated by testosterone. Thus the purpose of the present study was to determine whether endogenous testosterone regulates CASM ICa,L through regulation of VGCC expression and activity. Sexually mature male and female Yucatan swine (7–8 mo; 35–45 kg) were obtained from the breeder. Males were left intact (IM, n = 8), castrated (CM, n = 8), or castrated with testosterone replacement (CMT, n = 8; 10 mg/day Androgel). Females remained gonad intact ( n = 8). In right coronary arteries, both Cav1.2 mRNA and protein were greater in IM compared with intact females. Cav1.2 mRNA and protein were reduced in CM compared with IM and restored in CMT. In isolated CASM, both peak and steady-state ICa were reduced in CM compared with IM and restored in CMT. In males, a linear relationship was found between serum testosterone levels and ICa. In vitro, both testosterone and the nonaromatizable androgen, dihydrotestosterone, increased Cav1.2 expression. Furthermore, this effect was blocked by the androgen receptor antagonist cyproterone. We conclude that endogenous testosterone is a primary regulator of Cav1.2 expression and activity in coronary arteries of males.

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Voltage-Gated Potassium+ Channel Expression in Coronary Artery Smooth Muscle Cells of SHR and WKY

Cell Biochemistry and Biophysics ◽

10.1007/s12013-014-0120-4 ◽

2014 ◽

Vol 70 (3) ◽

pp. 1725-1731 ◽

Cited By ~ 1

Author(s):

Zhi Hu ◽

Aiqun Ma ◽

Yushun Zhang ◽

Yutao Xi ◽

Lihong Fan ◽

...

Keyword(s):

Smooth Muscle ◽

Coronary Artery ◽

Smooth Muscle Cells ◽

Potassium Channel ◽

Muscle Cells ◽

Voltage Gated ◽

Channel Expression

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Beraprost Upregulates KV Channel Expression and Function via EP4 Receptor in Pulmonary Artery Smooth Muscle Cells Obtained from Rats with Hypoxia-Induced Pulmonary Hypertension

Journal of Vascular Research ◽

10.1159/000500424 ◽

2019 ◽

Vol 56 (4) ◽

pp. 204-214 ◽

Cited By ~ 1

Author(s):

Hua Tian ◽

Fenling Fan ◽

Jie Geng ◽

Jizhao Deng ◽

Hongyan Tian

Keyword(s):

Pulmonary Hypertension ◽

Smooth Muscle ◽

Pulmonary Artery ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

Channel Expression ◽

Pulmonary Artery Smooth Muscle ◽

And Function

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Smooth muscle ATP-sensitive potassium channels mediate migraine-relevant hypersensitivity in mouse models

Cephalalgia ◽

10.1177/03331024211053570 ◽

2021 ◽

pp. 033310242110535

Author(s):

Sarah L Christensen ◽

Rikke H Rasmussen ◽

Sanne La Cour ◽

Charlotte Ernstsen ◽

Thomas F Hansen ◽

...

Keyword(s):

Smooth Muscle ◽

Mouse Models ◽

Ex Vivo ◽

Target Tissue ◽

Loss Of Function ◽

Dilatory Response ◽

Channel Opening ◽

Nociceptive Responses ◽

Channel Expression ◽

Mrna And Protein Expression

Background Opening of KATP channels by systemic levcromakalim treatment triggers attacks in migraine patients and hypersensitivity to von Frey stimulation in a mouse model. Blocking of these channels is effective in several preclinical migraine models. It is unknown in what tissue and cell type KATP-induced migraine attacks are initiated and which KATP channel subtype is targeted. Methods In mouse models, we administered levcromakalim intracerebroventricularly, intraperitoneally and intraplantarily and compared the nociceptive responses by von Frey and hotplate tests. Mice with a conditional loss-of-function mutation in the smooth muscle KATP channel subunit Kir6.1 were given levcromakalim and GTN and examined with von Frey filaments. Arteries were tested for their ability to dilate ex vivo. mRNA expression, western blotting and immunohistochemical stainings were made to identify relevant target tissue for migraine induced by KATP channel opening. Results Systemic administration of levcromakalim induced hypersensitivity but central and local administration provided antinociception respectively no effect. The Kir6.1 smooth muscle knockout mouse was protected from both GTN and levcromakalim induced hypersensitivity, and their arteries had impaired dilatory response to the latter. mRNA and protein expression studies showed that trigeminal ganglia did not have significant KATP channel expression of any subtype, whereas brain arteries and dura mater primarily expressed the Kir6.1 + SUR2B subtype. Conclusion Hypersensitivity provoked by GTN and levcromakalim in mice is dependent on functional smooth muscle KATP channels of extracerebral origin. These results suggest a vascular contribution to hypersensitivity induced by migraine triggers.

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