A-Type Potassium Current in Retinal Arteriolar Smooth Muscle Cells

McGahon, Mary K.; Dawicki, Jennine; Scholfield, C. Norman; McGeown, J. Graham; Curtis, Tim M.

doi:10.1167/iovs.04-1465

Cited by 25 publications

(34 citation statements)

References 28 publications

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“…Knowledge of the specific molecular mechanisms governing the phenotype and behavior of arteriolar smooth muscle cells is quite rudimentary when compared with that of many other cellular systems. Nevertheless, significant progress has been made, particularly toward understanding mechanisms of rhythmicity, myogenic tone, and ion transport (11,12,14,17,20,25,26,31,33,34). An area of particular interest is calcium signaling (10,15,26,38).…”

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confidence: 99%

E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles

Xu¹,

Boulay²,

Flemming³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. E3-targeted anti-TRPC5 antibody inhibits storeoperated calcium entry in freshly isolated pial arterioles. Am J Physiol Heart Circ Physiol 291: H2653-H2659, 2006. First published July 21, 2006 doi:10.1152/ajpheart.00495.2006.-Smooth muscle cells in arterioles have pivotal roles in the determination of blood pressure and distribution of local blood flow. The cells exhibit calcium entry in response to passive store depletion, but the mechanisms and relevance of this phenomenon are poorly understood. Previously, a role for canonical transient receptor potential 1 (TRPC1) was indicated, but heterologous expression studies showed TRPC1 to have poor function in isolation, suggesting a requirement for additional proteins. Here we test the hypothesis that TRPC5 is such an additional protein, because TRPC5 forms heteromultimeric channels with TRPC1, and RNA encoding TRPC5 is present in arterioles. Recordings were from arteriolar fragments freshly isolated from rabbit pial membrane. Ionic current in response to store depletion has properties like that of the TRPC1/TRPC5 heteromultimer, and so the effect of the E3-targeted, externally acting, anti-TRPC5 blocking antibody (T5E3) was explored. T5E3 suppressed calcium entry in store-depleted arterioles but had no effect in the absence of store depletion. T5E3 preadsorbed to its antigenic peptide did not inhibit calcium entry. TRPC6 is commonly detected in smooth muscle and is present in the arterioles, but T5E3 had no effect on TRPC6. The data suggest that calcium entry occurring in response to passive store depletion in smooth muscle cells of arterioles involves TRPC5 as well as TRPC1.arteriole; smooth muscle cell; calcium channel; store-operated channel; transient receptor potential; functional antibody ARTERIOLES ARE small precapillary arteries containing a single smooth muscle layer. Because of the small diameter and number of arterioles, they have a major impact on peripheral resistance and provide the primary structure regulating local blood flow according to metabolic needs of surrounding tissue.

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mentioning

confidence: 99%

E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles

Xu¹,

Boulay²,

Flemming³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…2B). However, the BK Ca channel blocker Penitrem A (500 nM) (35) or the K ATP channel blocker glyburide (10 M) did not affect the hypoxia-induced contraction (P Ͼ 0.05, n ϭ 12), thus suggesting a role for K v channel inhibition in the PV hypoxic contractile response.…”

Section: Resultsmentioning

confidence: 92%

“…This is consistent with observations made in murine PASMC, where the voltage window was narrower, between Ϫ40 and Ϫ10 mV, but the peak availability of Ϫ31.5 mV was similarly close to the RMP value of Ϫ27.9 mV (32). In smooth muscle from retinal arterioles, McGahon et al (35) have suggested that the A-type current is active at RMP and that its hyperpolarizing effect on the RMP suppresses membrane excitability. A similar role for K v in the rat PV is supported by the observation that application of 4-AP results in contraction (37).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia sensitivity of a voltage-gated potassium current in porcine intrapulmonary vein smooth muscle cells

Dospinescu

Widmer

Rowe

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Hypoxia contracts the pulmonary vein, but the underlying cellular effectors remain unclear. Utilizing contractile studies and whole cell patch-clamp electrophysiology, we report for the first time a hypoxia-sensitive K(+) current in porcine pulmonary vein smooth muscle cells (PVSMC). Hypoxia induced a transient contractile response that was 56 ± 7% of the control response (80 mM KCl). This contraction required extracellular Ca(2+) and was sensitive to Ca(2+) channel blockade. Blockade of K(+) channels by tetraethylammonium chloride (TEA) or 4-aminopyridine (4-AP) reversibly inhibited the hypoxia-mediated contraction. Single-isolated PVSMC (typically 159.1 ± 2.3 μm long) had mean resting membrane potentials (RMP) of -36 ± 4 mV with a mean membrane capacitance of 108 ± 3.5 pF. Whole cell patch-clamp recordings identified a rapidly activating, partially inactivating K(+) current (I(KH)) that was hypoxia, TEA, and 4-AP sensitive. I(KH) was insensitive to Penitrem A or glyburide in PVSMC and had a time to peak of 14.4 ± 3.3 ms and recovered in 67 ms following inactivation at +80 mV. Peak window current was -32 mV, suggesting that I(KH) may contribute to PVSMC RMP. The molecular identity of the potassium channel is not clear. However, RT-PCR, using porcine pulmonary artery and vein samples, identified Kv(1.5), Kv(2.1), and BK, with all three being more abundant in the PV. Both artery and vein expressed STREX, a highly conserved and hypoxia-sensitive BK channel variant. Taken together, our data support the hypothesis that hypoxic inhibition of I(KH) would contribute to hypoxic-induced contraction in PVSMC.

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“…I k is present in almost all types of vascular smooth muscle cells and is sensitive to TEA and/or 4-aminopyridine, depending on the cell type studied. However, it was determined that I A does coexist with I k in a few types of vascular smooth muscle cells including, renal (Gordienko et al, 1994), pulmonary (Iida et al, 2005) and retinal (McGahon et al, 2005) arteries. In addition, I A , i.e, A type K þ current, was reported to be the major K v current in retinal microvascular smooth muscle cells and played a physiological role in suppressing cell excitability as well as contractility (McGahon et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

NaHS induces relaxation response in prostaglandin F2α precontracted bovine retinal arteries partially via Kv and Kir channels

Takır

Ortaköylü

Toprak

et al. 2015

Experimental Eye Research

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A-Type Potassium Current in Retinal Arteriolar Smooth Muscle Cells

Abstract: A-type current is the major voltage-dependent K(+) current in retinal MVSM and appears to play a physiological role in suppressing cell excitability and contractility.

Cited by 25 publications

References 28 publications

E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles

E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles

Hypoxia sensitivity of a voltage-gated potassium current in porcine intrapulmonary vein smooth muscle cells

NaHS induces relaxation response in prostaglandin F2α precontracted bovine retinal arteries partially via Kv and Kir channels

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