Vascular Myocytes Research Articles

Warifteine, a bisbenzylisoquinoline alkaloid, induces relaxation by activating potassium channels in vascular myocytes

The present study used functional and electrophysiological approaches to investigate the mechanisms by which warifteine, a bisbenzylisoquinoline alkaloid isolated from Cissampelos sympodialis Eichl., causes vasorelaxation of the rat thoracic aorta. Warifteine (1 pmol/L-10 μmol/L) induced concentration-dependent relaxation (pD(2) = 9.40 ± 0.06; n = 5) of endothelium-intact aortic rings precontracted with noradrenaline (10-100 μmol/L). The relaxation effects were not attenuated by removal of the endothelium. Warifteine also induced the relaxation of prostaglandin F(2α) (1-10 mmol/L)-precontracted rings (pD(2) = 9.2 ± 0.2; n = 8). In contrast, the relaxant activity of warifteine was nearly abolished in high K(+) (80 mmol/L)-precontracted aortic rings. In preparations incubated with 20 mmol/L KCl or with the K(+) channel blockers tetraethylammonium (1, 3 and 5 mmol/L), iberiotoxin (20 nmol/L), 4-aminopyridine (1 mmol/L) or glibenclamide (10 μmol/L), the vasorelaxant activity of warifteine was markedly reduced. However, BaCl(2) (1 mmol/L) had no effect on the relaxant effects of warifteine. In vascular myocytes, warifteine (100 nmol/L) significantly increased whole-cell K(+) currents (at 70 mV). Under nominally Ca(2+) -free conditions, warifteine did not reduce extracellular Ca(2+) -induced contractions in rings precontracted with high K(+) or noradrenaline (100 μmol/L). Together, the results of the present study indicate that warifteine induces potent concentration-dependent relaxation in the rat aorta via an endothelium-independent mechanism that involves the activation of K(+) channels.

Development and Evaluation of Tocopherol-Rich Argan Oil-Based Nanoemulsions as Vehicles Possessing Anticancer Activity

In recent years, diverse nanoemulsion vehicles (NEs) have been developed with vast potential for improving therapeutic index of clinically approved and experimental drugs. Using oils rich in omega-3 and omega-6 polyunsaturated fatty acids (PUFA), several promising nanoemulsion formulations have been developed recently for oral and systemic administration. The aim of our present work is to successfully develop and characterize optimized nanoemulsion platform, using the PUFA-rich argan oil that contain several important anti-inflammatory and antimitotic natural components. Using various emulsifying mixtures of polyethoxylated solutol HS-15 and polyethyleneglucol Vitamin E succinyl ester (TPGS), to form different NEs showing extended shelf-life stability. The physicochemical properties of prototype argan NEs were analyzed and utilizing a 32 full factorial design, followed by biocompatibility screen, using normal vascular myocytes and areolar fibroblasts. While 90-180 day stability of NEs correlated with TPGS:solutol surfactant blend ratios, adverse effects on integrity of test cultures were only noted at high TPGS content in the emulsifier system, exceeding 80%. Finally, the anti-proliferative efficacy of selected stable and acceptably biocompatible nanoscale TPGS-emulsified argan oil formulations was investigated using murine breast and colon carcinoma cells. The IC50 values of the combination of argan oil and TPGS (40-80% wt of emulsifiers) were 5-9 folds lower compared to TPGS-free and argan-oil free control NEs. Argan oil NE, stabilized with Vitamin E TPGS and solutol HS mixtures, demonstrated significant pro-apoptotic effect on both test cancer cell lines, indicating built-in anticancer properties for such NE platform, potentially enhancing overall antineoplastic effects of incorporated candidate chemotherapeutic agents.

ARSENIC TRIOXIDE INHIBITS THE VOLTAGE-GATED K+ CHANNELS IN RAT MESENTERIC ARTERIAL SMOOTH MUSCLE CELLS

ARSENIC TRIOXIDE INHIBITS THE VOLTAGE-GATED K+ CHANNELS IN RAT MESENTERIC ARTERIAL SMOOTH MUSCLE CELLS

Abstract 144: Increased CaMKII Activity in Hypertensive Vascular Endothelium

The Ca2+-calmodulin dependent protein kinase II (CaMKII) plays a prime role in the development of cardiovascular diseases including heart failure and diabetes-associated vasculopathies. The multifunctional kinase can promote the genesis or sustainment of cardiovascular pathological conditions. Although the role of cardiac CaMKII is well established, literature on endothelial CaMKII is only emerging. Recent studies showed that CaMKII activation could alter expression and activity of enzymes such as eNOS suggesting that CaMKII might be involved in endothelial dysfunction. A better understanding of CaMKII signalling will lead to the improvement of cardiovascular therapies. CaMKII act as a Ca2+ sensor by its ability to decode oscillatory Ca2+ signalling through complex autophosphorylation steps. Such oscillatory Ca2+ signalling has only recently been reported in endothelium, the Ca2+ pulsars. The Ca2+ pulsars might represent a novel and distinctive activation mechanism for endothelial CaMKII. This study is aimed to elucidate the correlation between endothelial Ca2+ dynamics and CaMKII activity in microvasculature. PCR experiments showed that all four mammalian CaMKII isoforms are expressed in small murine mesenteric arteries but only variant 1 of CaMKIIβ have been identified. However, confocal microscopy revealed that only CaMKIIα, β and δ can be found in endothelial cells and only δ and γ in vascular myocytes. Moreover, α and β specifically converged at Ca2+ pulsar sites and stimulation of Ca2+ pulsars increased CaMKII clustering. Activated CaMKII (T286) also showed similar distribution. These evidences suggest that Ca2+ pulsars activate CaMKII. Our results showed that spontaneous Ca2+ pulsars are increased (54%) in arterial hypertension (AH) and can stimulate basal CaMKII activity. Indeed, CaMKII clustering is increased in AH (2 fold). However, an inverse correlation between CaMKIIβ expression and blood pressure was established (r2=0.6760), suggesting that blood pressure significantly alters expression of the kinase. This study demonstrates that CaMKII activity and expression is significantly modulated in hypertension and provides evidences that CaMKII represent an interesting therapeutic approach for vascular pathologies.

The Assessment of Endothelial Function

The discovery of nitric oxide (NO) as a crucial endothelium-derived molecule for vascular relaxation and the recognition of the endothelium as more than a passive interface between blood and the vessel wall led to substantial progress in the field of vascular research.1 Endothelial dysfunction is a pathological condition characterized mainly by an imbalance between substances with vasodilating, antimitogenic, and antithrombogenic properties (endothelium-derived relaxing factors)2 and substances with vasoconstricting, prothrombotic, and proliferative characteristics (endothelium-derived contracting factors).3 Among the most important vasodilator molecules, particularly in muscular arteries, is NO, which also inhibits other key events in the development of atherosclerosis such as platelet adhesion and aggregation, leukocyte adhesion and migration, and smooth muscle cell proliferation. Particularly in the microcirculation, prostacyclin and endothelium-derived hyperpolarization factors (an umbrella term for substances and signals hyperpolarizing vascular myocytes by opening voltage channels4) also play an important role. Generally, loss of NO bioavailability indicates a broadly dysfunctional phenotype across many properties of the endothelium. Thus, the assessment of its vasodilator properties resulting from NO and other molecules may provide information on the integrity and function of the endothelium. Interestingly, most, if not all, cardiovascular risk factors are associated with endothelial dysfunction,5 and risk factor modification leads to improvement in vascular function. Endothelial dysfunction has been detected in the coronary epicardial and resistance vasculature and in peripheral arteries, so endothelial dysfunction can be regarded as a systemic condition.6 Importantly, the process of atherosclerosis begins early in life, and endothelial dysfunction contributes to atherogenesis and precedes the development of morphological vascular changes.7 Over the past 25 years, many methodological approaches have been developed to measure the (patho)physiological function of the endothelium in humans.8 Although the ability to measure endothelial function has boosted clinical research in this field, its use as a …

Systemic Distribution of Viral Antigen in Alpacas Persistently Infected With Bovine Pestivirus

Recently, confirmed occurrences of persistent bovine viral diarrhea virus (BVDV) infection in North American alpacas have raised concerns about the role of persistently infected (PI) alpacas in transmission of virus among herds, yet only limited pathological descriptions of persistent infections in alpacas have been reported. The objective of this study was to characterize BVDV antigen distribution in 10 PI alpacas of varying age and to compare viral antigen distribution and localization in tissues of PI alpacas with 5 PI calves of varying age. Ocular dysplasia was evident in 1 PI alpaca, constituting the first reported congenital ocular lesion in PI alpacas. Viral antigen was widely distributed in alpaca tissues and was prominent in neurons, endothelial cells, and vascular tunica media myocytes but had limited distribution in lymphoid tissues and moderate distribution in epithelium of several organ systems of alpacas. Macrophages in the alpaca gastrointestinal system submucosa and lymph node medullary sinuses often had prominent labeling. In addition, only 1 alpaca had antigen labeling in the bone marrow in contrast to PI cattle. Labeled cells in calf tissues were more widely distributed, occurring prominently in lymphoid and epithelial tissues. Common features of the 2 host species were widespread antigen labeling and absence of lymphoid depletion.

Myoendothelial Junction Formation is Restricted in Pulmonary Arteries of Fetal Sheep

Endothelial cell activation can hyperpolarize vascular myocytes, resulting in myocyte relaxation and vessel dilation. Direct communication by way of myoendothelial junctions (MEJ) made through the internal elastic lamina (IEL) contributes to vasodilatory responses. The function of the MEJ in pulmonary arteries is not completely understood and less is known regarding their function before birth. The fetal lung has little blood flow and endothelium‐dependent relaxation of pulmonary arteries is limited, which lead us to hypothesize that MEJs are underdeveloped in the fetal lung. This hypothesis was tested using laser scanning confocal microscopy techniques and viewing the IEL of pulmonary arteries from fetal and adult sheep. The IEL was viewed using autofluorescence, and MEJ's were visualized using cell mask red fluorescence. The number and size of pores in the IEL were quantified to index potential MEJ sites and this was compared to the number of MEJ sites that stained positive for cell membrane. Preliminary data suggests the size of each IEL pore, total pore area, and percentage of IEL holes with MEJs was greater in the adult. The restricted IEL pore and MEJ formation in the fetus could diminish MEJ –dependent myocyte hyperpolarization and resultant vasodilation. This could contribute to the high vascular resistance in the fetal pulmonary vasculature. Support from HHMI, NIH and NSF.

Dysregulation of ryanodine receptors/Ca2+ release channels by FKBP12.6 in diabetic vascular myocytes

Diabetes significantly increases mortality and morbidity from accompanying cerebral and other vascular diseases, which may result from an abnormally enhanced increase in [Ca2+]i in vascular smooth muscle cells (SMCs). However, the underlying molecular processes remain unclear. Here, we for the first time show that the activity of ryanodine receptors/Ca2+ release channels (RyRs) is greatly enhanced in diabetic cerebral artery SMCs (CASMCs). RyR‐mediated local Ca2+ release (Ca2+ spark) is significantly increased. Targeted gene knockout of FK506 binding protein 12.6 (FKBP12.6−/−), known to associate with and inhibit (stabilize) RyR2, increases Ca2+ spark as well. However, the increased Ca2+ spark is not further augmented in FKBP12.6−/−/diabetic cells. Caffeine, a classic RyR agonist, evokes an equivalent enhanced increase in [Ca2+]i (global Ca2+ release) in diabetic, FKBP12.6−/−, and FKBP12.6−/−/diabetic CASMCs. The amount of FKBP12.6 is largely decreased in SR fractions from diabetic cerebral arteries, and increased in cytosolic fractions, suggesting FKBP12.6/RyR dissociation. Supportively, FKBP12.6/RyR2 FRET signal is significantly decreased in diabetic CASMCs. Collectively, we conclude that FKBP12.6/RyR2 dissociation represents an essential mechanism in the diabetic increase in [Ca2+]i in vascular SMCs and associated vascular diseases.

Hydrogen Sulfide as an Endothelium-Derived Hyperpolarizing Factor in Rodent Mesenteric Arteries

To the Editor: We read with interest the article by Mustafa et al1 in Circulation Research in which the authors suggest that hydrogen sulfide is a major endothelium-derived hyperpolarizing factor (EDHF) that generates endothelial and vascular myocyte hyperpolarization and relaxation by predominantly activating ATP-sensitive potassium channels (KATP) through cysteine S-sulfhydration. As previously reported by many groups, Mustafa et al1 confirm that endothelium-dependent cholinergic relaxations in murine mesenteric artery are minimally affected by combined inhibition of nitric oxide synthase and cyclooxygenase (L-NAME plus indomethacin), observations that are consistent with underlying EDHF-dependent mechanisms. However, it is important to stress that these data do not indicate that nitric oxide and prostacyclin pathways are poorly implicated because ACh-induced relaxations involve various overlapping endothelial mechanisms such that …

The steroid interaction site in transmembrane domain 2 of the large conductance, voltage- and calcium-gated potassium (BK) channel accessory β1 subunit

Large conductance, voltage- and calcium-gated potassium (BK) channels regulate several physiological processes, including myogenic tone and thus, artery diameter. Nongenomic modulation of BK activity by steroids is increasingly recognized, but the precise location of steroid action remains unknown. We have shown that artery dilation by lithocholate (LC) and related cholane steroids is caused by a 2× increase in vascular myocyte BK activity (EC(50) = 45 μM), an action that requires β1 but not other (β2-β4) BK accessory subunits. Combining mutagenesis and patch-clamping under physiological conditions of calcium and voltage on BK α- (cbv1) and β1 subunits from rat cerebral artery myocytes, we identify the steroid interaction site from two regions in BK β1 transmembrane domain 2 proposed by computational dynamics: the outer site includes L157, L158, and T165, whereas the inner site includes T169, L172, and L173. As expected from computational modeling, cbv1+rβ1T165A,T169A channels were LC-unresponsive. However, cbv1 + rβ1T165A and cbv1 + rβ1T165A,L157A,L158A were fully sensitive to LC. Data indicate that the transmembrane domain 2 outer site does not contribute to steroid action. Cbv1 + rβ1T169A was LC-insensitive, with rβ1T169S being unable to rescue responsiveness to LC. Moreover, cbv1 + rβ1L172A, and cbv1 + rβ1L173A channels were LC-insensitive. These data and computational modeling indicate that tight hydrogen bonding between T169 and the steroid α-hydroxyl, and hydrophobic interactions between L172,L173 and the steroid rings are both necessary for LC action. Therefore, β1 TM2 T169,L172,L173 provides the interaction area for cholane steroid activation of BK channels. Because this amino acid triplet is unique to BK β1, our study provides a structural basis for advancing β1 subunit-specific pharmacology of BK channels.

Reactive Oxygen Species-mediated TRPC6 Protein Activation in Vascular Myocytes, a Mechanism for Vasoconstrictor-regulated Vascular Tone

Both TRPC6 and reactive oxygen species (ROS) play an important role in regulating vascular function. However, their interplay has not been explored. The present study examined whether activation of TRPC6 in vascular smooth muscle cells (VSMCs) by ROS was a physiological mechanism for regulating vascular tone by vasoconstrictors. In A7r5 cells, arginine vasopressin (AVP) evoked a striking Ca(2+) entry response that was significantly attenuated by either knocking down TRPC6 using siRNA or inhibition of NADPH oxidases with apocynin or diphenyleneiodonium. Inhibition of TRPC6 or ROS production also decreased AVP-stimulated membrane currents. In primary cultured aortic VSMCs, catalase and diphenyleneiodonium significantly suppressed AVP- and angiotensin II-induced whole cell currents and Ca(2+) entry, respectively. In freshly isolated and endothelium-denuded thoracic aortas, hyperforin (an activator of TRPC6), but not its vehicle, induced dose- and time-dependent constriction in TRPC6 wide type (WT) mice. This response was not observed in TRPC6 knock-out (KO) mice. Consistent with the ex vivo study, hyperforin stimulated a robust Ca(2+) entry in the aortic VSMCs from WT mice but not from KO mice. Phenylephrine induced a dose-dependent contraction of WT aortic segments, and this response was inhibited by catalase. Moreover, H(2)O(2) itself evoked Ca(2+) influx and inward currents in A7r5 cells, and these responses were significantly attenuated by either inhibition of TRPC6 or blocking vesicle trafficking. H(2)O(2) also induced inward currents in primary VSMCs from WT but not from TRPC6 KO mice. Additionally, H(2)O(2) stimulated a dose-dependent constriction of the aortas from WT mice but not from the vessels of KO mice. Furthermore, TIRFM showed that H(2)O(2) triggered membrane trafficking of TRPC6 in A7r5 cells. These results suggest a new signaling pathway of ROS-TRPC6 in controlling vessel contraction by vasoconstrictors.

Reply to Chadha et al.

Reply to Chadha et al.

Modern views on amlodipine and new S-amlodipine medications

The review presents the latest evidence on the calcium antagonist amlodipine, summarizing its mechanisms of action, its pleiotropic, endothelial function-related effects, and its anti-atherogenic activity. Amlodipine suppresses the proliferation of vascular smooth myocytes and extracellular matrix and improves endothelial vasodilatation, despite the absence of L-type calcium channels in these cells. This mechanism is related to an increase in endothelial nitric oxide (NO) release. The results of experimental studies on the role of S and R amlodipine isomers in its hemodynamic and pleiotropic activity are presented. While S-amlodipine is a pharmacologically active blocker of L-type calcium channels, R-amlodipine increases endothelial NO release. New medications have been developed, based on S-amlodipine. It has been shown that S-amlodipine 5 mg/d is bioequivalent to amlodipine 10 mg/d. The pharmacodynamics analysis demonstrated that S-amlodipine 5 mg/d and amlodipine 10 mg/d did not differ significantly in terms of mean levels of systolic and diastolic blood pressure, or mean heart rate. S-amlodipine was better tolerated and characterised by a lower incidence of peripheral edema than amlodipine. However, the effects of S-amlodipine on hard end-points should be investigated in the long-term prospective studies.

Human Umbilical Cord Blood Stem Cells Secrete Growth Factors and Anti‐Inflammatory Cytokines that Protect Vascular Endothelial Cells and Cardiac Myocytes from Ischemia and Injury

Human Umbilical Cord Blood Stem Cells Secrete Growth Factors and Anti‐Inflammatory Cytokines that Protect Vascular Endothelial Cells and Cardiac Myocytes from Ischemia and Injury

Small and intermediate conductance Ca2+‐activated K+channels regulate spontaneous contraction of mouse portal vein myocytes

Ca2+‐activated K+ channels (KCa) are key components of vascular myocytes EC coupling through their control of smooth muscle cell membrane potential. Whilst BKCa is expressed ubiquitously in smooth muscle cells, only proliferative VSMCs express KCa3.1 channels. However, mouse portal vein (mPV) is an atypical blood vessel showing spontaneous and rhythmic contractions. Since KCa channels are involved in the regulation of excitability of other cell types like neurons, the contribution of KCa2.x and KCa3.1 channels to the control of mPV excitability was investigated. Expression of KCa2.x and KCa3.1 was detected in mPV by PCR and immunohistochemistry. In single cell patch clamp studies, the RMP of isolated mPV myocytes was hyperpolarized (≈15 mV) by exposure to NS309 (10 μM), a KCa2.x and KCa3.1 channel activator. Inhibition of KCa2.x channels with UCL1689 (3 μM) reversed the effect of NS309 whilst inhibition of KCa3.1 channels (TRAM‐34; 10 μM) had no effect. NS309 significantly decreased the amplitude and increased the frequency of spontaneous contractions of intact mPV. These effects were reversed by application of UCL1689, suggesting that the NS309‐induced changes in spontaneous mPV contractions is carried out by KCa2.x channels. This study suggest that KCa2.x and KCa3.1 channels are expressed in mouse portal vein myocytes and play an important role in regulation of spontaneous contractions.Supported by FICM

Expression of ATP-sensitive potassium channels in human pregnant myometrium

BackgroundPotassium channels play critical roles in the regulation of cell membrane potential, which is central to the excitability of myometrium. The ATP-sensitive potassium (KATP) channel is one of the most abundant potassium channels in myometrium. The objectives of this study were to investigate the protein expression of KATP channel in human myometrium and determine the levels of KATP channel in lower and upper segmental myometrium before and after onset of labour.MethodsBoth lower segmental (LS) and upper segmental (US) myometrial biopsies were collected at cesarean section from pregnant women not-in-labour (TNL) or in-labour (TL) at term. Protein expression level and cellular localization of four KATP channel subunits in US and LS myometrium were determined by Western blot analysis and immunohistochemistry, respectively. The contractile activity of myometrial strip was measured under isometric conditions.ResultsFour KATP channel subunits, namely Kir6.1, Kir6.2, SUR1 and SUR2B were identified in pregnant myometrium. While found in vascular myocytes, these subunits appear to be preferentially expressed in myometrial myocytes. Diazoxide, a KATP channel opener, inhibited the spontaneous contractility of pregnant myometrium, suggesting that the KATP channels are functional in human pregnant myometrium. Diazoxide was less potent in TL strips than that in TNL strips. Interestingly, expression of SUR1 was greater in TL than TNL tissues, although no differences were found for SUR2B in these two tissues. For both lower and upper segmental myometrium, Kir6.1 and Kir6.2 were less in TL compared with TNL tissues.ConclusionsFunctional KATP channels are expressed in human pregnant myometrium. Down-regulation of Kir6.1 and Kir6.2 expression in myometrium may contribute to the enhanced uterine contractility associated with the onset of labour.

Ca2+ entry following P2X receptor activation induces IP3 receptor-mediated Ca2+ release in myocytes from small renal arteries.

P2X receptors mediate sympathetic control and autoregulation of the renal circulation triggering contraction of renal vascular smooth muscle cells (RVSMCs) via an elevation of intracellular Ca(2+) concentration ([Ca(2+) ](i) ). Although it is well-appreciated that the myocyte Ca(2+) signalling system is composed of microdomains, little is known about the structure of the [Ca(2+) ](i) responses induced by P2X receptor stimulation in vascular myocytes. Using confocal microscopy, perforated-patch electrical recordings, immuno-/organelle-specific staining, flash photolysis and RT-PCR analysis we explored, at the subcellular level, the Ca(2+) signalling system engaged in RVSMCs on stimulation of P2X receptors with the selective agonist αβ-methylene ATP (αβ-meATP). RT-PCR analysis of single RVSMCs showed the presence of genes encoding inositol 1,4,5-trisphosphate receptor type 1(IP(3) R1) and ryanodine receptor type 2 (RyR2). The amplitude of the [Ca(2+) ](i) transients depended on αβ-meATP concentration. Depolarization induced by 10 µmol·L(-1) αβ-meATP triggered an abrupt Ca(2+) release from sub-plasmalemmal ('junctional') sarcoplasmic reticulum enriched with IP(3) Rs but poor in RyRs. Depletion of calcium stores, block of voltage-gated Ca(2+) channels (VGCCs) or IP(3) Rs suppressed the sub-plasmalemmal [Ca(2+) ](i) upstroke significantly more than block of RyRs. The effect of calcium store depletion or IP(3) R inhibition on the sub-plasmalemmal [Ca(2+) ](i) upstroke was attenuated following block of VGCCs. Depolarization of RVSMCs following P2X receptor activation induces IP(3) R-mediated Ca(2+) release from sub-plasmalemmal ('junctional') sarcoplasmic reticulum, which is activated mainly by Ca(2+) influx through VGCCs. This mechanism provides convergence of signalling pathways engaged in electromechanical and pharmacomechanical coupling in renal vascular myocytes.

Activation Mechanisms and Molecular Properties of Cyclopiazonic Acid (CPA)-Evoked TRPC Channels in Vascular Myocytes from TRPC1-/- Mice

Phosphatidyinositol-4,5-bisphosphate (PIP2) has an obligatory role in activating heteromeric TRPC1 subunit-containing channels in vascular myocytes, which also requires protein kinase C (PKC)-mediated phosphorylation of TRPC1 proteins. The aim of the present work was to further investigate these proposed activation mechanisms in freshly isolated mesenteric artery myocytes from TRPC1-/- mice.

PI3 Kinase-Mediated Pathways Activate TRPC Channels in Vascular Myocytes

It is generally thought that vasoconstrictors activate canonical transient receptor potential (TRPC) channels through stimulation of phospholipase-mediated pathways in vascular myocytes, with generation of diacylglycerol (DAG) being an essential event. TRPC1-containing channels are activated by DAG through a PKC-dependent pathway whereas non-TRPC1-containing channels (e.g. TRPC3/6/7) are gated by DAG via a PKC-independent mechanism. However, endothelin-1 (ET-1)-evoked TRPC1 and TRPC3/6/7 channels in rabbit coronary artery myocytes are not inhibited by phospholipase inhibitors, which indicates that other mechanism are involved in activating these channels.

Inhibition of TRPC6 Channels by TRPC1/C5 Channel Activity Through a Ca 2+ and Pkc-Dependent Mechanism

Vascular myocytes express two groups of functional canonical transient receptor (TRPC) channels, which we have termed TRPC1 for TRPC1-containing and TRPC3/6/7 for non-TRPC1 containing channels. These two groups have distinct properties from each other, for example, TRPC1 channels have a single unitary conductance of 2-3 pS and require PIP2 and PKC for activation, whereas TRPC3/6/7 channels have multiple conductances between 10-70 pS and are inhibited by PIP2 and PKC. The present work investigated interactions between TRPC1/C5 and TRPC6 channels activities evoked by angiotensin II (Ang II) in freshly isolated rabbit mesenteric artery myocytes.