Activators of voltage-dependent L-type calcium channels

The L class of voltage-dependent Ca²⁺ channels provides an important pathway for Ca²⁺ entry into a variety of excitable cells. Many drugs have been shown to be blockers of this channel including the clinically available nifedipine, verapamil, and diltiazem. An increasing number of compounds are now being recognized as activators of L-type Ca²⁺ channels. The best characterized of these are certain 1,4-dihydropyridines, typified by Bay K 8644, which act as partial agonists of the channel. The benzoylpyrrole group of molecules, which includes FPL 64176, have proven to be highly efficacious L channel agonists. Certain naturally occurring substances, ranging from toxins to endogenous ligands, have also been proposed as activators of this channel. Activators of L-type Ca²⁺ channels have proven to be valuable tools with which to study the structure and function of these channels and could lead to the development of new therapeutic entities. © 1994 Wiley-Liss, Inc.     

Modulation of intracellular calcium by potassium channel openers in vascular muscle

Summary We investigated two putative K⁺ channel openers, pinacidil and BRL34915 (cromakalim), and demonstrated their vasorelaxant effectiveness on rat artery contractions induced by K⁺, tetraethylammonium (TEA), or norepinephrine. The K⁺ channel opener-induced decrease in tension was rapid, even when tension was stimulated by 100 mmol/l K⁺. Measurements of intracellular free Ca⁺⁺ (activity) by ultra-high sensitivity digital imaging microscopy was carried out by briefly loaded fura2 (fluorescence ratio) quantitation in isolated, contracting cells of rat azygos vein. Submicron resolution was achieved by measuring cytoplasmic Ca⁺⁺-sensitive fluorescence at each pixel, and size and intensity of areas with high Ca⁺⁺ concentrations, called hot spots, were determined by a computer-generated, 3 algorithm. Hot spots, which most likely represent the sites of Ca⁺⁺ release and re-uptake by Ca⁺⁺-regulatory organelles, increased in size and intensity upon addition of K⁺ or norepinephrine, reaching an early peak prior to the whole cell average peak in cytoplasmic Ca⁺⁺ activity. Both norepinephrine and K⁺-induced stimulation resulted in Ca⁺⁺ activity increases that were primarily due to Ca⁺⁺ release from storage sites. Reduction of free Ca⁺⁺ activity to resting or lower levels occurred upon addition of pinacidil or cromakalim. Intracellular Ca⁺⁺ decreases due to K⁺ channel openers appeared abruptly beginning at the central portions of the cells, resulting in a pronounced early drop in central Ca⁺⁺ activity while elevated Ca⁺⁺ levels persisted at the periphery. While this late stage residual of peripheral Ca⁺⁺ appears to be a significant step in the vascular muscle relaxant action of both K⁺ channel opener drugs, the level of Ca⁺⁺ at peripheral sites was greater in response to pinacidil than to cromakalim. The results of this study suggest that in addition to increasing K⁺ conductance, pinacidil and cromakalim cause 1) decreased Ca⁺⁺ activity in central regions of the myocytes, and 2) a shift in Ca⁺⁺ distribution to primarily subsarcolemmal sites. These observations lead us to hypothesize separate control of peripheral and central Ca⁺⁺ activity within a vascular muscle cell, with Ca⁺⁺ redistribution that can be altered by vasorelaxants. We suggest that intracellular Ca⁺⁺ redistribution may contribute the membrane potential-independent part of the vasorelaxant action of the K⁺ channel openers.This study was supported by NIH grants HL38537 and HL38645, and Eli Lilly Co. P.E. was supported by the Swiss Foundation of Cardiology and by the SNF 32-029 975.90     

Intracellular influx of calcium induced by quartz particles in alveolar macrophages

Historical studies report that cellular injury and silicosis are related to cytosolic free calcium (Ca²⁺). Moreover, reactive oxygen species (ROS) have been linked to cellular injury. However, the detail mechanism of the increase in [Ca²⁺]_i and the relationship between [Ca²⁺]_i and ROS production remains unknown. Quartz particle has been found to increase [Ca²⁺]_i and activate the generation of ROS. Our hypothesis is that [Ca²⁺]_i increase induced by quartz particle is from extracellular Ca²⁺ through the Ca²⁺ channel, and [Ca²⁺]_i increase is believed to activate ROS production. In order to examine this hypothesis, we treated rat alveolar macrophages with quartz (SiO₂) particles and used laser scanning confocal microscopy to measure [Ca²⁺]_i and the fluorescence intensity of ROS. Time- and dose-dependent increases in [Ca²⁺]_I and ROS in macrophages as well as cell viability were observed. Through chelating extracellular Ca²⁺ with ethylene glycol tetraacetic acid and releasing intracellular Ca²⁺ with thapsigargin, we found that 72.7% of the [Ca²⁺]_i increase was due to the influx of Ca²⁺ from the extracellular environment, via Ca²⁺ channels in the plasma membrane. By adding mannitol to scavenge hydroxyl radicals (OH·), and removing surface iron from the quartz particles to reduce OH· generation, we observed a reduced level of ROS generation, whereas the increase in [Ca²⁺]_i was unaffected. When using EGTA to reduce [Ca²⁺]_i, we observed a decrease in ROS production. This study suggests that the [Ca²⁺]_i influx was independent of OH· production, and the [Ca²⁺]_i increase resulted in ROS production. These results further indicate that there is a strong relationship between cytosolic free Ca²⁺ content and cellular injury as well as silica exposure.     

Tetramethylpyrazine as potassium channel opener to lower calcium influx into cultured aortic smooth muscle cells

In the present study, the effect of tetramethylpyrazine (TMP) on calcium (Ca 2+) influx was investigated in cultured vascular smooth muscle (A7r5) cells using Fura-2 as an indicator. The increase of Ca 2+ concentration in A7r5 cells produced by vasopressin or phenylephrine was attenuated by TMP from 0.01 micromol/L to 1 mmol/L. The decrease in the intracellular potassium concentration in A7r5 cells by TMP from 0.01 micromol/L to 10 micromol/L was characterized using PBFI/AM. Inhibitors specific to the small conductance calcium-activated potassium (SKCa ) channel or the ATP-sensitive potassium (K ATP ) channel abolished the actions of TMP. The obtained results indicate that the decrease of Ca 2+ influx into A7r5 cells by TMP is mainly mediated by the opening of potassium channels.     

Glucosamine suppresses platelet-activating factor-induced activation of microglia through inhibition of store-operated calcium influx

Microglia activation and subsequent release of inflammatory mediators are implicated in the pathophysiology of neurodegenerative diseases. Platelet-activating factor (PAF), a potent lipid mediator synthesized by microglia, is known to stimulate microglia functional responses. In this study, we determined that endogenous PAF exert autocrine effects on microglia activation, as well as the underlying mechanism involved. We also investigated the effect of d-glucosamine (GlcN) on PAF-induced cellular activation in human HMO6 microglial cells. PAF induced sustained intracellular Ca²⁺ ([Ca²⁺]_i) increase through store-operated Ca²⁺ channels (SOC) and reactive oxygen species (ROS) generation. PAF also induced pro-inflammatory markers through NFκB/COX-2 signaling. GlcN significantly inhibited PAF-induced Ca²⁺ influx and ROS generation without significant cytotoxicity. GlcN downregulated excessive expression of pro-inflammatory markers and promoted filopodia formation through NFκB/COX-2 inhibition in PAF-stimulated HMO6 cells. Taken together, these data suggest that GlcN may offer substantial therapeutic potential for treating inflammatory and neurodegenerative diseases accompanied by microglial activation.     

Intracellular free calcium concentration in rat anterior pituitary cells as indicated by fura-2: effect of arginine-vasopressin

Summary Arginine-vasopressin (AVP) stimulates adrenocorticotropin and -endorphin release from corticotrophs of the anterior pituitary gland through mechanisms which are not initiated by an elevation of the cellular levels of adenosine-3,5-cyclic-monophosphate. In the present study the effect of AVP on the cytoplasmic concentrations of free calcium ions in rat anterior pituitary cells was examined. Cytosolic free Ca²⁺ concentrations were monitored directly using the new, intracellularly trapped fluorescent indicator fura-2. In cells incubated in medium containing 1.3 mmol/l Ca²⁺, AVP (100 nmol/l) caused an immediate elevation of the cytoplasmic Ca²⁺ concentration by about 50 nmol/l (P < 0.001). The intracellular Ca²⁺ levels remained elevated during the observation period of 2–3 min. This effect of AVP was blocked by a specific vasopressin antagonist. By contrast, the glucocorticoid dexamethasone did not affect the AVP-induced elevation of cytosolic Ca²⁺ concentration. When the cells were incubated in Ca²⁺-free medium (Ca²⁺ omitted, EGTA 2 mmol/l), the AVP-induced as well as the K⁺ depolarization-induced increase in free cytoplasmic Ca²⁺ were abolished, whereas the ionophore ionomycin evoked a rapid transient elevation of free Ca²⁺. The increase in cytoplasmic Ca²⁺ concentration induced by AVP was preserved in medium containing the calcium channel blockers Mg²⁺ (Mg²⁺ 31.2 mmol/l; Ca²⁺ 1.3 mmol/l) or nifedipine (1 mol/l). The potassium-evoked calcium signal was blocked by Mg²⁺ (31.2 mmol/l). We conclude that vasopressin induces a rapid rise in the cytoplasmic concentration of free calcium ions in corticotrophs. Vasopressin may mobilize calcium through mechanisms that neither are glucocorticoid-sensitive nor involve the influx of extracellular celcium through voltage-dependent calcium channels. The rise in Ca²⁺ concentration may be an early intracellular signal that links the cell-surface receptors for vasopressin to secretion of ACTH and -endorphin. Send offprint requests to W. Knepel     

Arachidonic acid elevates cytosolic free calcium concentration in rat anterior pituitary cells

Summary Arachidonic acid is liberated from phospholipids by various hypothalamic releasing hormones and may be involved in stimulus-secretion coupling in rat adenohypophysis. In the present study, the effect of exogenous arachidonic acid on calcium homeostasis in rat anterior pituitary cells was investigated in vitro. Arachidonic acid markedly stimulated the release of various anterior pituitary hormones (beta-endorphin, luteinizing hormone, growth hormone). Arachidonic acid (10 mol/l) decreased the initial rate of ⁴⁵Ca²⁺ uptake. In cells prelabelled with ⁴⁵Ca²⁺, arachidonic acid (10 mol/l) decreased the exchangeable cell calcium content and increased the rate of ⁴⁵Ca²⁺ extrusion. Cytosolic free calcium concentration ([Ca²⁺]_i) was measured with the fluorescent indicator fura-2. Arachidonic acid markedly elevated [Ca²⁺]_i. The concentration dependency of this effect (1 mol/l and above) was similar to that on hormone secretion. Arachidonic acid (6 mol/l) elevated [Ca²⁺]_i by about 300 nmol/l, and arachidonic acid (10 mol/l) raised [Ca²⁺]i i into the micromolar range. The effect of arachidonic acid (3 mol/l) on [Ca²⁺]_i was not influenced by inhibitors of arachidonic acid metabolism (nordihydroguaiaretic acid, BW755C). In Ca²⁺-free media (Ca²⁺ omitted, EGTA 2 mmol/l), the effect of arachidonic acid (3 mol/l) on [Ca²⁺]_i was almost unimpaired, whereas the effect of arachidonic acid (10 mol/l) was reduced. Thus, the secretagogue arachidonic acid induces calcium mobilization and an increase in cytosolic free calcium concentration. These actions further qualify arachidonic acid as a potential intracellular mediator of stimulus-induced hormone secretion from rat adenohypophysis.This work was supported by the Deutsche Forschungsgemeinschaft (Kn 220/1-2) Send offprint requests to W. Knepel.     

Effect of tetramethylpyrazine on potassium channels to lower calcium concentration in cultured aortic smooth muscle cells

1. Tetramethylpyrazine (TMP) is one of the active principles contained in Ligusticum chuanxiong Hort. (Umbelliferae), a herb that has been used widely in China to treat vascular disorders. 2. In an attempt to elucidate the possible mechanisms of action of TMP, the effect of TMP on intracellular calcium concentrations ([Ca2+]i) was investigated in cultured vascular smooth muscle (A7r5) cells using the Ca(2+)-sensitive dye Fura-2 as an indicator. 3. The increase in [Ca2+]i in A7r5 cells produced by vasopressin (1 micromol/L) or phenylephrine (1 micromol/L) was attenuated by TMP in a concentration-dependent manner. Only inhibitors specific to ATP-sensitive potassium (KATP) channels or small conductance calcium-activated potassium (SKCa) channels attenuated the action of TMP (10 micromol/L) on [Ca2+]i. However, blockers of other K+ channels failed to modify the inhibitory action of TMP (10 micromol/L) on [Ca2+]i. 4. The action of TMP on membrane potential in A7r5 cells was monitored by the fluorescence of bisoxonol. Tetramethylpyrazine caused a concentration-dependent inhibition of changes in membrane potential elicited by KCl (20 mmol/L) or phenylephrine (1 micro mol/L), an effect that was totally reversed by glibenclamide (100 micromol/L) and apamin (100 nmol/L) in combination. 5. The results obtained indicate that the decrease in [Ca2+]i in A7r5 cells produced by TMP is mediated mainly by opening of KATP and/or SKCa channels.     

铅对小鼠海马[Ca2+]的影响及L型钙通道的作用

目的　探讨铅对分离的小鼠海马细胞内游离钙的影响及其及L型钙通道的作用。方法　采用低浓度胰蛋白酶消化法分离小鼠海马细胞 ,并以莹光指标剂 (Fura 2 )作Ca2 荧光探针 ,用双波长荧光法测定海马细胞 [Ca2 ] i。结果　铅可致分离的小鼠海马细胞 [Ca2 ] i 升高 [由静息时的 (2 0 3 4± 10 86)nmol L升至 (4 2 3 3± 19 2 6)nmol L] ,而不论胞外是否有钙 ;铅可抑制钾诱发海马细胞 [Ca2 ] i 升高 ,尼莫地平可加强这种抑制作用 ,而BayK864 4则可部分消除这种抑制作用。结论　铅可致分离的小鼠海马细胞 [Ca2 ] i 升高作用与胞内钙库释放有关 ;铅的抑制钾诱发海马细胞 [Ca2 ] i 升高作用与其抑制L型钙通道有关。     

Coupling factor 6 as a novel vasoactive and proatherogenic peptide in vascular endothelial cells

Coupling factor 6 (CF6) is composed of 76 amino acids and is present in the peripheral stalk of mitochondrial ATP synthase. The generation of CF6 is positively regulated by tumor necrosis factor α and shear stress via nuclear factor κB, and by high glucose via protein kinase C and p38 mitogen-activated protein kinase. CF6 is released outside of the cells from vascular endothelial cells, and binds to the β-subunit of the plasma membrane-bound ATP synthase in vascular endothelial cells and leads to intracellular acidosis. CF6 produces vasoconstriction, and the biological active site resides at the C-terminal portion. CF6 suppresses prostacyclin generation via inhibition of cytosolic phospholipase A₂. CF6 also suppresses nitric oxide synthase activity via an increase in asymmetric dimethylarginine and a decrease in platelet/endothelial cell adhesion molecule-1. CF6 induces the gene and protein expression of proatherogenic molecules such as endothelin 2, urokinase type plasminogen activator receptor, estrogen receptor β, a soluble short form of vascular endothelial growth factor receptor-1, and lectin-like oxidized low-density lipoprotein receptor-1. The plasma level of CF6 is elevated in patients with essential hypertension, diabetes mellitus, end-stage renal disease, acute myocardial infarction, and coronary heart disease. It is likely that CF6 contributes to the pathogenesis of cardiovascular diseases, but further intensive investigation is needed.     

钙通道阻滞剂对大鼠肝细胞钙释放激活的钙电流的影响(英文)

目的:研究钙通道拮抗剂对大鼠肝细胞钙释放激活的钙电流(I_(CRAC))的影响,方法:应用全细胞膜片箝技术。结果:I_(CRAC)的电流峰值是(-0.41±0.09)nA(n=15),反转电位约为0 mV,维拉帕米(Ver),地尔硫(艹卓)(Dil)和硝苯地平(Nif)显著降低I_(CRAC),不影响它的反转电位,Ver 5 μmol·L~(-1)的抑制率是40％±12％(n=3),Ver 50 μmol·L~(-1)使,CRAC的幅值从(-0.49±0.12)nA降到(-0.20±0.09)nA(n=5,P<0.01),抑制率为57％±15％,Dil和Nif 50 μmol·L~(-1)分别从(-0.43±0.10)nA(n=5),(-0.32±0.08)nA(n=5)降到(-0.29±0.07)nA(P<0.01),(-0.27±0.08)nA(P<0.01),抑制率分别为31％±11％,19％±7％,I_(CRAC)的幅值大小依赖细胞外钙浓度。I_(CRAC)在含台氏液1.8 mmol·L~(-1)中电流幅值为(-0.21±0.08)nA(n=3,P<0.01),结论:这三种钙通道拮抗剂有效抑制,I_(CRAC)并且通过抑制I~(CRAC)减少肝细胞钙超载。     

去极化作为电压门控性钙通道的调节信号

去极化作为电压门控性钙通道的调节信号ＤａｖｉｄＪＴＲＩＧＧＬＥ（Ｄｅａｎ，ＴｈｅＧｒａｄｕａｔｅＳｃｈｏｏｌ，ＳｔａｔｅＵｎｉｖｅｒｓｉｔｙｏｆＮｅｗＹｏｒｋ，ＢｕｆｆａｌｏＮＹ１４２６０，ＵＳＡ）关键词钙通道；膜电位；神经生理学；电生理学；钙通道激...     

小剂量缓激肽对大鼠脑微血管内皮细胞和C6细胞钙激活钾电流的作用

目的研究小剂量缓激肽对大鼠脑血管内皮细胞和C6细胞钙激活钾电流的作用。方法应用膜片钳全细胞记录模式。结果指令电位为+60 mV时,1μmol.L-1缓激肽可使大鼠脑血管内皮细胞和C6细胞钙激活钾电流分别由给药前的(770±220)pA和(630±220)pA降至给药后的(370±40)pA和(308±19)pA(n=6,P<0.01)。结论小剂量的缓激肽通过抑制脑微血管内皮细胞和C6细胞的钙激活性钾电流,引起细胞的去极化。     

丹酚酸B镁盐抑制低氧诱导内皮细胞钙内流和一氧化氮释放

AIM: To investigate the inhibitory effect of magnesium lithospermate B (MLB) on hypoxia-induced elevation of intracellular calcium concentration ([Ca2+]i) and nitric oxide (NO) release in endothelial cells. METHODS: The cultured human umbilical vein endothelial cells (ECV304) were cultured for 30 min under 95 % N(2) and 5 % CO2. Cell injury was evaluated by dye exclusion test and lactate dehydrogenase (LDH) assay. [Ca2+]i was determined by Fura 2-AM. NO content was examined by the NO assay kit. Endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) mRNA expressions were measured by semi-quantitative RT-PCR. RESULTS: Cell viability was decreased from (93.0 +/- 2.6) % in normoxia to (85.5 +/- 2.1) % in hypoxia (P < 0.01), and LDH release was increased from (41 +/- 28) U/L in normoxia to (141+/-68) U/L in hypoxia (P < 0.01) in ECV304 cultured under calcium conditions. MLB 5 and 10 mg/L improved cell viability and inhibited LDH leakage in ECV304. In addition, hypoxia increased [Ca2+]i, NO release, and eNOS and iNOS mRNA expressions in ECV304 (P < 0.01). These increases could be inhibited by MLB 5 and 10 mg/L (P < 0.01), but they were unaffected by hypoxia under calcium-free conditions. CONCLUSION: MLB attenuates hypoxia-induced cell injury and inhibits hypoxia-induced increases of [Ca2+]i, NO release, and eNOS and iNOS mRNA expressions in ECV304 in Krebs'solution containing calcium. The decreases of NO production and eNOS mRNA expression are possibly associated with inhibition of extracellular calcium influx in MLB-treated ECV304     

Genetically targeted calcium sensors enhance the study of organelle function in living cells

1. Understanding the regulation of calcium (Ca2+), the most common of the mineral ions within the human body, has always been of extreme interest to physiologists. While the importance of Ca2+ in contributing to physiological events through regulation of levels has been significantly established, seldom is consideration given to the intricacies of this ion and its mechanics in producing such diverse physiological responses in different regions of the cell. 2. The present review will summarize new methodologies used in our laboratories for the study of two major intracellular organelles, mitochondria and the nucleus. These techniques are based predominantly on the use of molecular biological approaches to both create and then target protein-based sensor molecules to specific intracellular locations. 3. The regulation of Ca2+ in the mitochondria and nucleus is of particular interest to us because of the central involvement of these organelles in: (i) cardiac cell responses during ischaemia/reperfusion; and (ii) the control of gene expression, respectively.     

Dual effects of tetrandrine on calcium activated potassium channels in pulmonary artery smooth muscle cells

目的：研究粉防己碱（Ｔｅｔ）对大鼠肺动脉平滑肌细胞钙激活钾（ＫＣａ）通道的影响．方法：内面朝外膜片箝单通道记录法．结果：Ｔｅｔ７５和１５μｍｏｌ·Ｌ－１使ＫＣａ的开放概率由０２５１±００１２增加到０３４０±００１３和０４１５±００１１（Ｐ＜００１）．关闭时间由（６１±１５）ｍｓ缩短到（３３±１０）和（２８±１１）ｍｓ（Ｐ＜００１）．Ｔｅｔ３０μｍｏｌ·Ｌ－１使开放概率和开放时间分别降低到（０１１４±０００８）和（１４７±００９）ｍｓ（Ｐ＜０．０１）．结论：Ｔｅｔ对大鼠肺动脉平滑肌细胞ＫＣａ通道有双重作用．     

大鼠肺动脉平滑肌细胞培养及对不同类型激动剂刺激产生的反应

目的分离和培养SD大鼠肺动脉平滑肌细胞（PASMCc）,并检测其功能状态。方法显微分离肺内小动脉,并在含胶原酶（1750 U&#183;mL^-1）和木瓜蛋白酶（9．5U&#183;mL^-1）的低钙HBSS溶液中酶解和培养PASMCs,采用动态细胞荧光成像技术检测PASMCs胞浆游离Ca^2＋浓度（[Ca^2＋]i）的变化。结果在18～24h内可获得PASMCs,并可观察到环匹阿尼酸和5-HT可引起PASMCs[Ca^2＋]i的升高效应。结论大鼠PASMCs一步酶消化法,方法简便实用。所分离的PASMCs细胞形态和功能正常,适用于动态细胞荧光成像技术检测实验及PASMCs信号转导功能的研究。     

Calcium signalling by G protein-coupled sphingolipid receptors in bovine aortic endothelial cells

Besides its role as a putative second messenger releasing Ca²⁺ from intracellular stores, sphingosine-1-phosphate (SPP) has recently been identified as an extracellularly acting ligand activating a high affinity G protein-coupled membrane receptor in various cell types. Since SPP can be released from activated platelets, we examined in the present study whether endothelial cells express receptors for SPP and related sphingolipids. In bovine aortic endothelial cells loaded with fura-2, addition of SPP caused a rapid and transient increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i), amounting to maximally about 230 nM. Removal of extracellular Ca²⁺ revealed that SPP-induced [Ca²⁺]_i elevations were due to both release of Ca²⁺ from intracellular stores and influx of extracellular Ca²⁺. Pretreatment of the cells with pertussis toxin inhibited the SPP-induced increase in [Ca²⁺]_i by 83%, in line with the previously reported involvement of G proteins of the G_i/o family in SPP signalling in other cell types. In contrast to other [Ca²⁺]_i-elevating agonists, e.g., ATP and bradykinin, SPP did not activate phospholipase C in bovine aortic endothelial cells, suggesting the involvement of a novel, unidentified signalling pathway in SPP-induced release of intracellular Ca²⁺. Furthermore, SPP also did not cause activation of either phospholipase D or A₂. Out of various related sphingolipids studied, only sphingosylphosphorylcholine (SPPC) induced a similar maximal increase in [Ca²⁺ _i as SPP, and its effect was also fully pertussis toxin-sensitive. However, the potencies of the two sphingolipids to increase [Ca²⁺]_i differed by more than two orders of magnitude, with the EC₅₀ values being 0.8 nM and 260 nM for SPP and SPPC, respectively. These results identify SPP and SPPC as novel and potent endothelial agonists, inducing calcium signalling by activation of a G_i/o protein-coupled receptor(s). Given the recently reported release of SPP from thrombin-activated platelets, SPP may represent a novel mediator of platelet-endothelial cell interactions.     

粉防己碱对大鼠肺动脉平滑肌细胞小电导钙激活钾通道的作用

目的　研究粉防己碱 (Tet)对大鼠肺动脉平滑肌细胞小电导钙激活钾通道 (SKCa)的作用。方法　内面朝外膜片箝单通道记录法。结果　Tet 7 5 μmol·L-1对电导值为 10pS的SKCa无明显影响 ,15 μmol·L-1可增加SKCa开放的概率 ,改变通道的开放和关闭模式 ,30 μmol·L-1降低通道的开放概率 ,通道开放以短暂簇状为主。结论　Tet对肺动脉平滑肌SKCa的作用与Tet的浓度有关 ,合适浓度下可增加通道的开放 ,K+ 外流增多 ,与Tet降低肺动脉张力有关。