Activation of high conductance Ca2+-activated K+ channels by sodium tanshinoneII-A sulfonate (DS-201) in porcine coronary artery smooth muscle cells

Yang, Yan; Cai, Fang; Li, Pengyun; Li, Miaoling; Chen, Jun; Chen, Guilan; Liu, Zhifei; Zeng, Xiaorong

doi:10.1016/j.ejphar.2008.09.013

Cited by 40 publications

(43 citation statements)

References 35 publications

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“…Whole-cell current, STOCs, single-channel current, and macromembrane current of BK Ca channels were recorded in human VSMCs with the techniques as described previously 15,16 and in the online-only Data Supplement Methods.…”

Section: Electrophysiologymentioning

confidence: 99%

Function of BK _Ca Channels Is Reduced in Human Vascular Smooth Muscle Cells From Han Chinese Patients With Hypertension

Yang

Cheng

et al. 2013

Hypertension

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It is well known that chronic hypertension is associated with increased morbidity and mortality from stroke, coronary artery disease, congestive heart failure, renal disease, and so on.1,2 Arterial tone is persistently increased as a result of malfunction of vessel relaxation in chronic hypertension.2 It is well recognized that arterial tone is regulated by functional balance of the ion channels responsible for cellular depolarization and hyperpolarization. The increased arterial tone is mainly related to depolarization of smooth muscle, which may have resulted from dysfunction of ion channels responsible for cell membrane hyperpolarization. 3 The membrane depolarization activates voltage-dependent l-type Ca 2+ channels, induces an increase in Ca 2+ influx and global intracellular Ca 2+ level, and causes vessel constriction. 4,5 It is believed that large-conductance Ca 2+ -activated K + (BK Ca ) channels play an important role in hyperpolarization of vascular smooth muscle cells (VSMCs).6 BK Ca channels are activated by intracellular local Ca 2+ release events through ryanodine receptors (Ca 2+ sparks) from the sarcoplasmic reticulum and subsequently induce a hyperpolarization that opposes vasoconstriction. 6-8The Ca 2+ sparks are highly localized and short-lived Ca 2+ transients, which is a local Ca 2+ signaling to induce spontaneous transient outward currents (STOCs) in VSMCs and neurons, and mediate different physiological functions. 8,9 In VSMCs, functional coupling of sparks to STOCs hyperpolarizes the membrane potential, which in turn closes the voltage-dependent l-type Ca 2+ channels, decreases global [Ca 2+ ] i , and induces vascular relaxation. 7 Studies from animal models demonstrated that a reduced activity of Ca 2+ sparks and STOCs is involved in an increase of vascular tone in hypertension. [10][11][12] However, little information is available in literature regarding BK Ca channel activity in human arterial cells/tissue from patients with hypertension. The present study was therefore to investigate whether BK Ca activity is altered in VSMCs isolated from mesentery arterial tissues of Han Chinese patients with hypertension using approaches of electrophysiology and molecular biology.Abstract-Chronic hypertension is associated with an impaired vascular relaxation caused by an increased vascular tone; however, the underlying mechanisms are not fully understood in human patients. The present study was to investigate whether large-conductance Ca 2+-and voltage-activated K + (BK Ca ) channels are involved in dysfunctional relaxation of artery in Han Chinese patients with hypertension using the perforated patch clamp, inside-out single-channel, and macromembrane patch recording techniques to determine whole-cell current, spontaneous transient outward current, open probability, and Ca 2+ sensitivity and the reverse transcription polymerase chain reaction and Western blot analysis to examine the gene and protein expression of α-subunit (KCa1.1) and β1-subunit (KCNMB1) of BK Ca channels in isolated human ...

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Section: Electrophysiologymentioning

confidence: 99%

Function of BK _Ca Channels Is Reduced in Human Vascular Smooth Muscle Cells From Han Chinese Patients With Hypertension

Yang

Cheng

et al. 2013

Hypertension

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“…Danshen has long been extensively used in improving body functions, such as promoting circulation and improving blood flow (12,13). Danshen and its various formula products in numerous pharmaceutical dosage forms are commercially available and are commonly administered to treat inflammatory and cardiovascular diseases in the clinics in China with negligible adverse effects (14)(15)(16)(17). STS has been clinically used in Asian countries for the prevention and treatment of coronary heart disease (18).…”

Section: Abstract: Sts; Trpc; Soce; Pulmonary Hypertensionmentioning

confidence: 99%

Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

Wang

Qian

Wan

et al. 2013

Am J Respir Cell Mol Biol

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Danshen, the dried root of Salvia miltiorrhiza, is widely used in clinics in China for treating various diseases, including cardiovascular diseases. Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA isolated as the major active component from Danshen, was recently reported to be effective in attenuating the characteristic pulmonary vascular changes associated with chronically hypoxic pulmonary hypertension (CHPH); however, the underlying detailed mechanisms are poorly understood. In this study, we investigated the effects of STS on basal intracellular Ca 21 concentration ([Ca 21 ] i ) and store-operated Ca 21 entry (SOCE) in distal pulmonary arterial smooth muscle cells (PASMCs) exposed to prolonged hypoxia or isolated from CHPH rats. SOCE measured by Mn 21 quenching of Fura-2 fluorescence in PASMCs from rats exposed to chronic hypoxia (10% O 2 , 21 d) was increased by 59%, and basal [Ca 21 ] i was increased by 119%; this effect was inhibited by intraperitoneal injection of STS. These inhibitory effects of STS on hypoxic increases of SOCE and basal [Ca 21 ] i were associated with reduced expression of canonical transient receptor potential (TRPC)1 and TRPC6 in distal pulmonary arterial smooth muscle and decreases on right ventricular pressure, right ventricular hypertrophy, and peripheral pulmonary vessel thickening. In ex vivo cultured distal PASMCs from normoxic rats, STS (0-25 mM) dose-dependently inhibited hypoxiainduced cell proliferation and migration, paralleled with attenuation in increases of basal [Ca 21 ] i , SOCE, mRNA, and protein expression of TRPC1 and TRPC6. STS also relieved right ventricular systolic pressure, right ventricular hypertrophy, and TRPC1 and TRPC6 protein expression in distal pulmonary arteries in a monocrotaline-induced rat model of pulmonary arterial hypertension. These results indicate that STS prevents pulmonary arterial hypertension development likely by inhibiting TRPC1 and TRPC6 expression, resulting in normalized basal [Ca 21 ] i and attenuated proliferation and migration of PASMCs.Keywords: STS; TRPC; SOCE; pulmonary hypertension Pulmonary arterial hypertension (PAH) is a rare yet life-threatening disease that affects 15 per 1 million adults, according to the most recent estimation in 2008 (1). It is physiologically defined by mean pulmonary arterial pressure of 25 mm Hg or greater at rest and is pathologically characterized by pulmonary vascular remodeling, including smooth muscle hypertrophy and intima thickening. Although significant progress has been made in the past decades in our understanding of PAH and in disease management, the prognosis is still poor, with a 1-year survival rate of 91.0% (2) and 3-year survival rate of 77% or less according to recent investigations (3-5). The principal treatments for PAH rely on approaches targeting the prostacyclin, endothelin, or NO pathways (phosphodiesterase inhibition) or, increasingly, on a combination of them (6-11). Few patients show indication for treatment with calcium channel...

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“…Currently known targets of TIIAS include Ca 21 -activated potassium channels and carboxylesterase 2, which are affected at similar or higher TIIAS concentrations as needed to strongly inhibit P2X7 (Yang et al, 2008b;Hatfield et al, 2013). In addition, a protection from LPS-induced acute lung injury by TIIAS has been demonstrated by Xu et al (2009).…”

Section: Discussionmentioning

confidence: 99%

Tanshinone II A Sulfonate, but Not Tanshinone II A, Acts as Potent Negative Allosteric Modulator of the Human Purinergic Receptor P2X7

Kaiser

Sobottka

Fischer

et al. 2014

J Pharmacol Exp Ther

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Tanshinone II A sulfonate (TIIAS) was identified as a potent, selective blocker of purinergic receptor P2X7 in a compound library screen. In this study, a detailed characterization of the pharmacologic effects of TIIAS on P2X7 is provided. Because TIIAS is a derivative of tanshinone II A (TIIA) and both compounds have been used interchangeably, TIIA was included in some assays. Fluorometric and electrophysiologic assays were used to characterize effects of TIIAS and TIIA on recombinantly expressed human, rat, and mouse P2X7. Results were confirmed in human monocyte-derived macrophages expressing native P2X7. In all experiments, involvement of P2X7 was verified using established P2X7 antagonists. TIIAS, but not TIIA, reduces Ca 21 influx via human P2X7 (hP2X7) with an IC 50 of 4.3 mM. TIIAS was less potent at mouse P2X7 and poorly inhibited rat P2X7. Monitoring of YO-PRO-1 uptake confirmed these findings, indicating that formation of the hP2X7 pore is also suppressed by TIIAS. Electrophysiologic experiments revealed a noncompetitive mode of action. TIIAS time-dependently inhibits hP2X7 gating, possibly by binding to the intracellular domain of the receptor. Inhibition of native P2X7 in macrophages by TIIAS was confirmed by monitoring Ca 21 influx, YO-PRO-1 uptake, and release of the proinflammatory cytokine interleukin-1b. Fluorometric experiments involving recombinantly expressed rat P2X2 and human P2X4 were conducted and verified the compound's selectivity. Our data suggest that hP2X7 is a molecular target of TIIAS, but not of TIIA, a compound with different pharmacologic properties.

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Activation of high conductance Ca2+-activated K+ channels by sodium tanshinoneII-A sulfonate (DS-201) in porcine coronary artery smooth muscle cells

Cited by 40 publications

References 35 publications

Function of BK _Ca Channels Is Reduced in Human Vascular Smooth Muscle Cells From Han Chinese Patients With Hypertension

Function of BK _Ca Channels Is Reduced in Human Vascular Smooth Muscle Cells From Han Chinese Patients With Hypertension

Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

Tanshinone II A Sulfonate, but Not Tanshinone II A, Acts as Potent Negative Allosteric Modulator of the Human Purinergic Receptor P2X7

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Activation of high conductance Ca2+-activated K+ channels by sodium tanshinoneII-A sulfonate (DS-201) in porcine coronary artery smooth muscle cells

Cited by 40 publications

References 35 publications

Function of BK Ca Channels Is Reduced in Human Vascular Smooth Muscle Cells From Han Chinese Patients With Hypertension

Function of BK Ca Channels Is Reduced in Human Vascular Smooth Muscle Cells From Han Chinese Patients With Hypertension

Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

Tanshinone II A Sulfonate, but Not Tanshinone II A, Acts as Potent Negative Allosteric Modulator of the Human Purinergic Receptor P2X7

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Function of BK _Ca Channels Is Reduced in Human Vascular Smooth Muscle Cells From Han Chinese Patients With Hypertension

Function of BK _Ca Channels Is Reduced in Human Vascular Smooth Muscle Cells From Han Chinese Patients With Hypertension