Ca(2+)‐activated Cl‐ and K+ channels and their modulation by endothelin‐1 in rat pulmonary arterial smooth muscle cells

Salter, KJ; Turner, JL; Albarwani, Sulayma; Kozlowski, Roland Z.

doi:10.1113/expphysiol.1995.sp003889

Cited by 27 publications

(19 citation statements)

References 16 publications

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“…Previous studies have indicated that the activation of ET-1 receptors mobilizes intracellular Ca ϩϩ stores in nonerythroid cells, [35][36][37][38] but whether cytosolic Ca ϩϩ in red cells is affected by ET-1 is unknown. Other intracellular signaling mechanisms that mediate ET-1 actions include phospholipase C, diacylglycerol, and PKC.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Gardos channel activity by cytokines in sickle erythrocytes

Rivera

Jarolím

Brugnara

2002

Blood

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It has recently been shown that the Gardos channel activity of mouse erythrocytes can be modified by endothelins, suggesting a functional linkage between endothelin receptors and the Gardos channel. Using 86 Rubidium ( 86 Rb) influx, effects were estimated of proinflammatory molecules such as platelet activator factor (PAF), endothelin-1 (ET-1), interleukin-10 (IL-10), and regulated on activation normal T cells expressed and secreted (RANTES) on the Gardos channel activity in human normal and sickle red cells. It was found that PAF (EC 50 : 15 ؎ 7 nM), RANTES (EC 50 , 9 ؎ 6 ng/mL [1.2 ؎ 0.8 nM]), IL-10 (EC 50 , 11 ؎ 8 ng/mL [204 ؎ 148 nM]), and ET-1 (EC 50 , 123 ؎ 34 nM) induce a significant increase in Gardos channel activity-between 28% and 84%-over the control. In addition, these agents modify the Gardos channel affinity for internal Ca ؉؉ (K 0.5 ) by 2-to 6-fold. Biochemical evidence is provided for the presence of ET receptor subtype B in sickle and normal red cells. Furthermore, it was found that ET-1, PAF, RANTES, and IL-10 induce a significant increase in red cell density (P < .05). These data suggest that activation of the Gardos channel is functionally coupled to receptor motifs such as C-X-C (PAF), C-C (RANTES), and ET receptor subtype B. Thus, cell volume regulation or erythrocyte hydration states might be altered by activation of the Gardos channel by cytokines in vivo. The role of these mediators in promoting sickle cell dehydration in vivo is under investigation. IntroductionSickle cell disease is characterized by chronic hemolytic anemia, frequent infection, and occlusion of the microcirculation that result in organ damage and painful episodes. Plasma levels of several proinflammatory and adhesive cytokines have been shown to be increased in sickle cell disease. [1][2][3][4][5] However, little is known about their contribution to its pathogenesis, though a relationship between adhesiveness of the sickle cells and the clinical state of the patients has been observed. 6 It has been postulated that factors that activate vascular endothelium may enhance the attachment of young reticulocytes and sickle cells to the endothelium and may cause delays in the passage of red cells through the microcirculation. 7,8 The prolonged microvascular transit time of sickle red cells may then provide the necessary time for hemoglobin polymerization, cell sickling, and vaso-occlusion to occur. 9 Red cell sickling and adhesion are favored by cellular dehydration, which increases the rate of hemoglobin polymerization and cell sickling. 10 Previous data have shown that the dehydration of sickle erythrocytes mediated by the Ca ϩϩ -activated K ϩ channel (Gardos channel) can be activated in vitro by oxygenationdeoxygenation cycles. 11 Blockade of the Gardos channel by clotrimazole induces a reduction in red cell dehydration in vivo and in vitro. 12,13 We postulated that activators of the Gardos channel might favor the formation of dense sickle cells and cell entrapment in the microvasculature. The arachidonic acid derivati...

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Section: Discussionmentioning

confidence: 99%

Modulation of Gardos channel activity by cytokines in sickle erythrocytes

Rivera

Jarolím

Brugnara

2002

Blood

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“…To compare the ability of a range of nucleotides to activate oscillatory inward currents, membrane current elicited over a 1-minute period was digitized at 100 Hz and integrated (pClamp software; version 6.2), as previously described, 25 giving a value in nA ⅐ ms. Contractions were normalized and expressed as N/mm 2 . Data are presented throughout as meanϮSEM.…”

Section: Discussionmentioning

confidence: 99%

Functional Evidence for a Novel Suramin-Insensitive Pyrimidine Receptor in Rat Small Pulmonary Arteries

Hartley

Kato

Salter

et al. 1998

Circulation Research

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Uridine nucleotides are known to cause constriction of pulmonary arterial smooth muscle. However, the P2 receptor subtypes underlying the contractile effects of these nucleotides in the pulmonary circulation have not been determined. We have used myography and the patch-clamp recording technique to compare the effects of UTP and UDP in isolated small pulmonary arteries (diameter 100 to 400 microm) and their constituent smooth muscle cells. In endothelium-denuded arteries, both UTP and UDP (0.01 to 3 mmol/L) induced concentration-dependent increases in tension that were independent of P2X receptor stimulation. The UDP-mediated increase in tension was significantly less sensitive to the nonselective P2 receptor blocker suramin than the UTP-mediated increase in tension. In single isolated arterial myocytes, voltage-clamped at -50 mV (close to the resting membrane potential of these cells), application of both UTP and UDP evoked periodic oscillations of inward current primarily because of a Ca2+-activated Cl- current (ICl,Ca). Oscillations of ICl,Ca evoked by UTP were reversibly inhibited by suramin, although those evoked by UDP were insensitive to the antagonist. In addition to confirming the presence of classical P2Y2 receptors, these results also provide functional evidence for the existence of a novel UDP receptor in pulmonary arterial myocytes, which may contribute to pyrimidine-evoked vasoconstriction. This notion is supported by molecular evidence that demonstrates the presence of P2Y6 receptor transcripts in rat pulmonary arterial smooth muscle.

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“…Inward Cl − currents (due to Cl − efflux) are enhanced by α-adrenergic stimulation in rabbit portal vein myocytes (13), by endothelin-1 or angiotensin II in rat pulmonary artery myocytes (20,45,46), and by endothelin-1 or vasopressin in A7r5 cells (56). Furthermore, the stimulation of Cl − efflux has been implicated in the vasoconstrictor effects of endothelin-1 in rabbit basilar artery (10) and norepinephrine in rat resistance arteries (33) and aorta (32).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells

Brueggemann¹,

Moran²,

Barakat³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

121

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[Arg 8 ]-vasopressin (AVP), at low concentrations (10-500 pM), stimulates oscillations in intracellular Ca 2+ concentration (Ca 2+ spikes) in A7r5 rat aortic smooth muscle cells. Our previous studies provided biochemical evidence that protein kinase C (PKC) activation and phosphorylation of voltage-sensitive K + (K v ) channels are crucial steps in this process. In the present study, K v currents (I Kv ) and membrane potential were measured using patch clamp techniques. Treatment of A7r5 cells with 100 pM AVP resulted in significant inhibition of I Kv . This effect was associated with gradual membrane depolarization, increased membrane resistance, and action potential (AP) generation in the same cells. The AVP-sensitive I Kv was resistant to 4-aminopyridine, iberiotoxin, and glibenclamide but was fully inhibited by the selective KCNQ channel blockers linopirdine (10 μM) and XE-991 (10 μM) and enhanced by the KCNQ channel activator flupirtine (10 μM). BaCl 2 (100 μM) or linopirdine (5 μM) mimicked the effects of AVP on K + currents, AP generation, and Ca 2+ spiking. Expression of KCNQ5 was detected by RT-PCR in A7r5 cells and freshly isolated rat aortic smooth muscle. RNA interference directed toward KCNQ5 reduced KCNQ5 protein expression and resulted in a significant decrease in I Kv in A7r5 cells. I Kv was also inhibited in response to the PKC activator 4β-phorbol 12-myristate 13-acetate (10 nM), and the inhibition of I Kv by AVP was prevented by the PKC inhibitor calphostin C (250 nM). These results suggest that the stimulation of Ca 2+ spiking by physiological concentrations of AVP involves PKC-dependent inhibition of KCNQ5 channels and increased AP firing in A7r5 cells.Keywords potassium channel; signal transduction; membrane potential; calcium; vascular smooth muscle; M current Vasoconstrictor hormones cause contraction of vascular smooth muscle (VSM) cells by increasing cytosolic free Ca 2+ concentration ([Ca 2+ ] i ), which in turn activates the cells' contractile apparatus. Voltage-sensitive L-type Ca 2+ channels are known to be important in vasoconstrictor action (27), although the signaling pathways leading to activation of L-type channels are not well characterized. Influx of Ca 2+ via L-type channels is enhanced by NIH Public Access Author ManuscriptAm J Physiol Heart Circ Physiol. Author manuscript; available in PMC 2008 November 3. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript membrane depolarization, which may result from activation of nonselective cation currents (34,47,54) or Cl − currents (30). Alternatively, inhibition of outward K + currents could provide a depolarizing stimulus for activation of L-type Ca 2+ channels (38).We have previously demonstrated that concentrations of [Arg 8 ]-vasopressin (AVP) that may be found in the systemic circulation (10-500 pM) modulate the frequency of L-type Ca 2+ channel-dependent Ca 2+ spikes in A7r5 rat aortic smooth muscle cells. The stimulation of Ca 2+ -dependent action potentials, which underlie AVP-stimulated...

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Ca(2+)‐activated Cl‐ and K+ channels and their modulation by endothelin‐1 in rat pulmonary arterial smooth muscle cells

Cited by 27 publications

References 16 publications

Modulation of Gardos channel activity by cytokines in sickle erythrocytes

Modulation of Gardos channel activity by cytokines in sickle erythrocytes

Functional Evidence for a Novel Suramin-Insensitive Pyrimidine Receptor in Rat Small Pulmonary Arteries

Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells

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