Plasticity of KIR channels in human smooth muscle cells from internal thoracic artery

2003 ◽  
Vol 284 (6) ◽  
pp. H2325-H2334 ◽  
Author(s):  
Tom Karkanis ◽  
Shaohua Li ◽  
J. Geoffrey Pickering ◽  
Stephen M. Sims
Keyword(s):  
Smooth Muscle ◽  
Current Density ◽  
Internal Thoracic Artery ◽  
Smooth Muscles ◽  
Vascular Smooth Muscles ◽  
Rt Pcr ◽  
Regulation Of Proliferation ◽  
Negative Membrane Potential ◽  
Inwardly Rectifying ◽  
Contractile Cells

Inwardly rectifying K+ (KIR) currents are present in some, but not all, vascular smooth muscles. We used patch-clamp methods to examine plasticity of this current by comparing contractile and proliferative phenotypes of a clonal human vascular smooth muscle cell line. Hyperpolarization of cells under voltage clamp elicited a large inward current that was selective for K+ and blocked by Ba2+. Current density was greater in proliferative compared with contractile cells (−4.5 ± 0.9 and −1.4 ± 0.3 pA/pF, respectively; P < 0.001). RT-PCR of mRNA from proliferative cells identified transcripts for Kir2.1 and Kir2.2 but not Kir2.3 potassium channels. Western blot analysis demonstrated greater expression of Kir2.1 protein in proliferative cells, consistent with the higher current density. Proliferative cells displayed a more negative membrane potential than contractile cells (−71 ± 2 and −35 ± 4 mV, respectively; P < 0.001). Ba2+ depolarized all cells, whereas small increases in extracellular K+ concentration elicited hyperpolarization only in contractile cells. Ba2+ inhibited [3H]thymidine incorporation, indicating a possible role for KIR channels in the regulation of proliferation. The phenotype-dependent plasticity of KIR channels may have relevance to vascular remodeling.

Regional variation in myosin isoforms and phosphorylation at the resting tone in urinary bladder smooth muscle

2001 ◽  
Vol 280 (2) ◽  
pp. C254-C264 ◽  
Author(s):  
Joseph A. Hypolite ◽  
Michael E. DiSanto ◽  
Yongmu Zheng ◽  
Shaohua Chang ◽  
Alan J. Wein ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Smooth Muscles ◽  
Urinary Continence ◽  
Myosin Isoforms ◽  
Bladder Smooth Muscle ◽  
Rt Pcr ◽  
Total Rna ◽  
Bladder Dome ◽  
Significant Difference

Urinary bladder filling and emptying requires coordinated control of bladder body and urethral smooth muscles. Bladder dome, midbladder, base, and urethra showed significant differences in the percentage of 20-kDa myosin light chain (LC20) phosphorylation (35.45 ± 4.6, 24.7 ± 2.2, 13.6± 2.1, and 12.8 ± 2.7%, respectively) in resting muscle. Agonist-mediated force was associated with a rise in LC20 phosphorylation, but the extent of phosphorylation at all levels of force was less for urethral than for bladder body smooth muscle. RT-PCR and quantitative competitive RT-PCR analyses of total RNA from bladder body and urethral smooth muscles revealed only a slight difference in myosin heavy chain mRNA copy number per total RNA, whereas mRNA copy numbers for NH2-terminal isoforms SM-B (inserted) and SM-A (noninserted) in these muscles showed a significant difference (2.28 × 108 vs. 1.68 × 108 for SM-B and 0.12 × 108 vs. 0.42 × 108 for SM-A, respectively), which was also evident at the protein level. The ratio of COOH-terminal isoforms SM2:SM1 in the urethra was moderately but significantly lower than that in other regions of the bladder body. A high degree of LC20phosphorylation and SM-B in the bladder body may help to facilitate fast cross-bridge cycling and force generation required for rapid emptying, whereas a lower level of LC20 phosphorylation and the presence of a higher amount of SM-A in urethral smooth muscle may help to maintain the high basal tone of urethra, required for urinary continence.

The Haemodynamic Consequences of Adaptive Structural Changes of the Resistance Vessels in Hypertension

1971 ◽  
Vol 41 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Björn Folkow
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Muscle Activity ◽  
Flow Resistance ◽  
Smooth Muscles ◽  
Vascular Smooth Muscles ◽  
Resistance Increase ◽  
Vascular Bed ◽  
Resistance Vessels ◽  
Vascular Beds

It is generally accepted that a rise in systemic flow resistance constitutes the essential background of the increased arterial blood pressure in well-established hypertension, though the early ‘labile’ phases of essential hypertension in particular may exhibit a pattern simulating a moderately intense defence reaction, with enhanced cardiac output and muscle blood flow as the most characteristic features, apart from the rise in blood pressure. With respect to the increased flow resistance in the well-established phase, it is accepted that the vessels respond readily, and apparently normally, to vasodilator substances, from which the correct conclusion has been drawn that the resistance increase cannot be ascribed to any sclerotic narrowing of the resistance vessels (Pickering, 1968). However, this observation has also generally led to the assumption that an increased smooth-muscle tone of the resistance vessels must be the explanation of the increased flow resistance and, despite the fact that there are numerous reports of medial hypertrophy in the precapillary resistance vessels for instance (Pickering, 1968), the possible haemodynamic consequences of such a type of structural vascular adaptation has hardly been considered at all. Instead the debate has mainly been concerned about whether the assumed increase of vascular tone is due to enhanced myogenic activity, to an increased neurogenic and/or hormonal exogenous stimulation of the vascular smooth muscles or whether these muscles might exhibit an enhanced sensitivity or ‘reactivity’ to such extrinsic stimuli. In other words, if summarized in a diagram relating the extent of active smooth-muscle shortening to the degree of resistance increase in an idealized resistance vessel (Fig. 1), an increased smooth muscle activity, whatever its background, would mean a shift from the normal resting equilibrium at point O to a point B along the curve N. However, one cannot safely deduce levels of vascular smooth-muscle activity between different individuals, or vascular beds, by simply assuming that they are proportional to the respective levels of current flow resistance. In each individual, or vascular bed, one must first relate the actual resistance level to that present when the vascular smooth muscles are completely inactive; i.e. when the resistance vessels are maximally dilated and exposed to the same amount of distending pressure. This latter resistance value provides the necessary ‘baseline’, or an equivalent of fully relaxed muscle length for a particular vascular bed, from which its current level of smooth muscle activity has to be judged in terms of the ratio between these two resistance values. This is simple and straightforward reasoning, but surprisingly enough studies along these lines were apparently not performed systematically until our group used this approach in analyses of the level of ‘basal tone’ in different vascular beds or individuals (Celander & Folkow, 1953; Löfving & Mellander, 1956; Folkow, 1956).

scholarly journals Endurance exercise training restores atrophy-induced decreases of myogenic response and ionic currents in rat skeletal muscle artery

2019 ◽  
Vol 126 (6) ◽  
pp. 1713-1724 ◽  
Author(s):  
Ming Zhe Yin ◽  
Hae Jin Kim ◽  
Eun Yeong Suh ◽  
Yin Hua Zhang ◽  
Hae Young Yoo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Exercise Training ◽  
Smooth Muscles ◽  
Ionic Currents ◽  
Myogenic Response ◽  
Mrna Levels ◽  
Voltage Gated ◽  
The Impact ◽  
Inwardly Rectifying ◽  
Channel Currents

Atrophic limbs exhibit decreased blood flow and histological changes in the arteries perfusing muscles. However, the effect of atrophy on vascular smooth muscle function is poorly understood. Here, we investigated the effect of unilateral sciatic denervation on the myogenic response (MR) and the ionic currents in deep femoral artery (DFA) smooth muscles from Sprague-Dawley rats. Because denervated rats were capable of treadmill exercise (20 m/min, 30 min, 3 times/wk), the impact of exercise training on these effects was also assessed. Skeletal arteries were harvested 3 or 5 wk after surgery. Then skeletal arteries or myocytes were subjected to video analysis of pressurized artery, myography, whole-cell patch clamp, and real-time quantitative PCR to determine the effect of hindlimb paralysis in the presence/absence of exercise training on MR, contractility, ionic currents, and channel transcription, respectively. In sedentary rats, atrophy was associated with loss of MR in the DFA at 5 wk. The contralateral DFA had a normal MR. At 5 wk after surgery, DFA myocytes from the atrophic limbs exhibited depressed L-type Ca2+currents, GTPγS-induced transient receptor potential cation channel (TRPC)-like currents, 80 mM KCl-induced vasoconstriction, TRPC6 mRNA, and voltage-gated K+and inwardly rectifying K+currents. Exercise training abrogated the differences in all of these functions between atrophic side and contralateral side DFA myocytes. These results suggest that a probable increase in hemodynamic stimuli in skeletal artery smooth muscle plays an important role in maintaining MR and ionic currents in skeletal artery smooth muscle. This may also explain the observed benefits of exercise in patients with limb paralysis.NEW & NOTEWORTHY Myogenic responses (MRs) in rat skeletal arteries feeding the unilateral atrophic hindlimb were impaired. In addition, the L-type Ca2+channel current, the TRPC6-like current, and TRPC6 mRNA levels in the corresponding myocytes decreased. Voltage-gated K+channel currents and inwardly rectifying K+channel currents were also attenuated in atrophic side myocytes. Exercise training effectively abrogated electrophysiological dysfunction of atrophic side myocytes and prevented loss of the MR.

Ca2+ coupling in vascular smooth muscle: Mg2+ and buffer effects on contractility and membrane Ca2+ movements

1982 ◽  
Vol 60 (4) ◽  
pp. 459-482 ◽  
Author(s):  
B. M. Altura ◽  
B. T. Altura ◽  
A. Carella ◽  
P. D. M. V. Turlapaty
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Reactivity ◽  
Smooth Muscles ◽  
Muscle Cells ◽  
Vascular Smooth Muscles ◽  
Disease States ◽  
Naturally Occurring ◽  
Ca Uptake ◽  
Coupling Processes

An examination of the literature, over the past two decades, reveals that (1) in studies of different types of vascular smooth muscles, Mg2+ is often either left out of physiological salt solutions or reduced in concentration compared with that in blood; and (2) when excitation–contraction coupling processes have been examined in isolated vascular tissues and cells, a number of artificial (synthetic) amine and organic zwitterion buffers have often been substituted for the naturally occurring bicarbonate and phosphate anions found in the blood and in cells. The influence of extracellular magnesium ions ([Mg2+]o) on tone, contractility, reactivity, and divalent cation movements in vascular smooth muscles, and how they may relate to certain vascular disease states, is reviewed. Data are presented and reviewed which indicate that many of the most commonly used artificial buffers (e.g., Tris. HEPES, MOPS, Bicine, PIPES, imidazole) can exert adverse effects on contractility and reactivity of certain arterial and venous smooth muscles. The data reviewed herein suggest that [Mg2+]o and membrane Mg are important in the regulation of vascular tone, vascular reactivity, and in control of Ca uptake, content, and distribution in smooth muscle cells. [Formula: see text] and (or) PO42−anions may be important for normal maintenance of excitability and reactivity and in the control of Ca uptake, content, and distribution in smooth muscle cells.

Decrease in activity of smooth muscle L-type Ca2+ channels and its reversal by NF-κB inhibitors in Crohn's colitis model

2003 ◽  
Vol 285 (3) ◽  
pp. G483-G493 ◽  
Author(s):  
Kazuya Kinoshita ◽  
Koichi Sato ◽  
Masatoshi Hori ◽  
Hiroshi Ozaki ◽  
Hideaki Karaki
Keyword(s):  
Smooth Muscle ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Current Density ◽  
Smooth Muscles ◽  
Circular Muscle ◽  
Rat Colon ◽  
Trinitrobenzenesulfonic Acid ◽  
Circular Smooth Muscle ◽  
Colonic Cells

We investigated the mechanisms of dysmotility of the colonic circular muscle of the Crohn's disease rat model. Contractions induced by KCl, carbachol, and Bay K 8644 were decreased in circular smooth muscles isolated from 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat colon. However, the absolute force and Ca2+ sensitivity of contractile proteins were not affected as assessed in α-toxin permeabilized smooth muscle. The current density of the L-type Ca2+ channel in circular smooth muscle cells was significantly decreased in the TNBS-treated colonic cells. However, expressions of the L-type Ca2+ channel mRNA and protein did not differ between control and TNBS-treated preparations. Pretreatment with the NF-κB inhibitors pyrrolidinedithiocarbamate and sulfasalazine partially recovered the decreased contractility and current density of the L-type Ca2+ channel by TNBS treatment. These results suggest that the decrease in the contraction of circular smooth muscle isolated from TNBS-induced colitis rat colon, which may be related to gut dysmotility in Crohn's disease, is attributable to the decreased activity of the L-type Ca2+ channel. The dysfunction of the L-type Ca2+ channel may be mediated by NF-κB-dependent pathways.

Inhibitory actions of a series of Ca2+ channel antagonists against agonist and K+ depolarization induced responses in smooth muscle: an assessment of selectivity of action

1986 ◽  
Vol 64 (3) ◽  
pp. 273-283 ◽  
Author(s):  
F. B. Yousif ◽  
D. J. Triggle
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Basic Structure ◽  
Similar Data ◽  
Induced Responses ◽  
Taenia Coli ◽  
Vascular Smooth Muscles ◽  
Inhibitory Effects ◽  
Tissue Selectivity

The inhibitory effects of the Ca2+ channel antagonists D-600, diltiazem, nifedipine and seven 1,4-dihydropyridine analogs of nifedipine against 80 mM K+ depolarization induced responses in guinea pig trachea, parenchyma, and pulmonary artery and rat renal and mesenteric artery preparations were determined. Together with similar data previously obtained for guinea pig ileum and bladder, these data permitted an assessment of tissue selectivity of action in smooth muscles of a series of Ca2+ channel antagonists under constant conditions (saline composition) and an identical challenge (K+ depolarization). Very similar rank orders of activity were expressed in all tissues suggesting that the same basic structure–activity relationship operates. However, the series of antagonists were significantly less active in respiratory smooth muscle than in other visceral or vascular smooth muscles. pA2 values for a series of 1,4-dihydropyridine antagonists measured in guinea pig taenia coli against Ca2+-induced responses in K+-depolarizing media correlated with mean inhibitory concentration values against K+-induced responses, suggesting that the latter were an appropriate measure of antagonist potency. pA2 values measured for nifedipine, D-600, and diltiazem against Ca2+-induced responses in taenia coli in the presence of a depolarizing K+ saline, or methylfurmethide, histamine, or 5-hydroxytryptamine did not differ, suggesting that the same channels were activated regardless of stimulant.

Expression of myosin isoforms in smooth muscle cells in the corpus cavernosum penis

1998 ◽  
Vol 275 (4) ◽  
pp. C976-C987 ◽  
Author(s):  
Michael E. DiSanto ◽  
Ze Wang ◽  
Chandrakala Menon ◽  
Yongmu Zheng ◽  
Thomas Chacko ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Amino Acid ◽  
Smooth Muscles ◽  
Corpus Cavernosum ◽  
Muscle Cells ◽  
Myosin Isoforms ◽  
Bladder Smooth Muscle ◽  
Rt Pcr ◽  
Two Dimensional Gel Electrophoresis ◽  
Resting Tone

Corpus cavernosum smooth muscle (CCSM) in the penis is unique in that it exhibits a high resting tone and, on stimulation, the muscle cells relax, allowing cavernous spaces to fill with blood, which results in an erection (tumescence). During detumescence, the muscle cells contract and return to the state of high resting tone. This study was undertaken to determine whether CCSM with these unique properties contains myosin isoforms typical of aorta or bladder smooth muscles, muscles that exhibit tonic and phasic characteristics, respectively. RT-PCR revealed that normal CCSM contains an SM2/SM1 mRNA ratio of 1.2:1 (similar to the rabbit aorta). Approximately 31% of the myosin heavy chain transcripts possess a 21-nt insert (predominant in bladder smooth muscle but not expressed in aorta) that encodes the seven-amino acid insert near the NH2-terminal ATP binding region in the head portion of the myosin molecule found in SMB, with the remaining mRNA being noninserted (SMA). Quantitative competitive RT-PCR revealed that the CCSM possesses ∼4.5-fold less SMB than the bladder smooth muscle. Western blot analysis using an antibody specific for the seven-amino acid insert reveals that both SM1 and SM2 in the CCSM contain the seven-amino acid insert. Furthermore, SMB containing the seven-amino acid insert was localized in the CCSM by immunofluorescence microscopy using this highly specific antibody. The analysis of the expression of LC17isoforms a and b in the CCSM revealed that it is similar to that of bladder smooth muscle. Thus the CCSM possesses an overall myosin isoform composition intermediate between aorta and bladder smooth muscles, which generally express tonic- and phasiclike characteristics, respectively. Two-dimensional gel electrophoresis showed a relatively low level (∼10%) of Ca2+-dependent light-chain (LC20) phosphorylation at the basal tone, which reaches ∼23% in response to maximal stimulation. The presence of noninserted and inserted myosin isoforms with low and high levels of actin-activated ATPase activities, respectively, in the CCSM may contribute to the ability of the CCSM to remain in a state of high resting tone and to relax rapidly for normal penile function.

scholarly journals Fluorescence demonstration of dipeptidyl peptidase II in skeletal, cardiac, and vascular smooth muscles.

1981 ◽  
Vol 29 (5) ◽  
pp. 672-677 ◽  
Author(s):  
W T Stauber ◽  
S H Ong
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Extensor Digitorum Longus ◽  
Smooth Muscles ◽  
Dipeptidyl Peptidase ◽  
Extensor Digitorum ◽  
Vascular Smooth Muscles ◽  
Normal Muscle ◽  
Muscle Tissues ◽  
Muscle Types

Dipeptidyl peptidase II (Dpp II) was demonstrated histochemically in soleus, extensor digitorum longus, cardiac, and vascular smooth muscle tissues using Lys-Ala-4-methoxy-beta-naphthylamide or Lys-Pro-4-methoxy-beta-naphthylamide as the substrate. The enzyme was found to be localized in discrete granules in all muscle types, but varied in its apparent activity. Dpp II activity was greatest in cardiac and least in extensor digitorum longus muscles with activity in soleus and vascular smooth muscles in between these extremes. Since Dpp II is localized only in lysosomes, the relative amounts and locales of lysosomes can be easily observed in normal muscle cells by the techniques described in this study.

Differentiation of mechanisms for mobilization of calcium in smooth muscle

1987 ◽  
Vol 65 (4) ◽  
pp. 724-728 ◽  
Author(s):  
George B. Weiss ◽  
Hideaki Karaki ◽  
Kazuyasu Murakami
Keyword(s):  
Smooth Muscle ◽  
Rate Coefficient ◽  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Vascular Smooth Muscles ◽  
Aortic Smooth Muscle ◽  
Renal Vessels ◽  
Experimental Approaches ◽  
Cellular Ca ◽  
Muscle Specificity

Techniques to dissociate different sites or stores important for Ca2+ entry or release in smooth muscle include washouts of 45Ca in cold La3+-substituted solutions, Scatchard-coordinate plots of Ca2+ uptake, substitution of Sr2+ for Ca2+, and both desaturation and rate coefficient plots. Rabbit aortic smooth muscle is particularly useful because Ca2+ mobilization components can be clearly separated. Other vascular preparations investigated (e.g., renal vessels, coronary arteries) appear to have similar components, but their relative importance varies. Respiratory smooth muscle also has similar Ca2+ mobilization components, but they are less readily dissociated by techniques employed in vascular smooth muscles. In guinea pig trachea, cold La3+ washouts do not retain cellular Ca2+ as well as in other preparations; use of other experimental approaches including the Ca2+ channel entry stimulator, CGP 28392, can demonstrate different Ca2+ uptake mechanisms for K+-stimulated and agonist-induced Ca2+ uptake. In rabbit aorta, CGP 28392 potentiates tension increases elicited with lower concentrations of added K+ but has no effect on norepinephrine-induced contraction. A general model illustrating different Ca2+ entry mechanisms present in three types of smooth muscle provides examples drawn from a spectrum of possible variations in smooth muscle specificity for Ca2+ mobilization.

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