The Role of K+and Cl−Channels in the Regulation of Retinal Arteriolar Tone and Blood Flow

Needham, Maurice; McGahon, Mary K.; Bankhead, Peter; Gardiner, Tom; Scholfield, C.N.; Curtis, Tim M.; McGeown, J. Graham

doi:10.1167/iovs.13-12948

Cited by 11 publications

(10 citation statements)

References 50 publications

(87 reference statements)

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“…In rabbits, 50 nmol/L iberiotoxin had no effect on resting pial arteriolar diameter, whereas 100 nmol/L produced only a 3% constriction (1371). In fawn hooded rats, administration of penetrem A or iberiotoxin into eyes results in no significant change in retinal arteriolar diameter, although both produced a 10% decrease in arteriolar blood flow, which was computed from the vessel diameter and red blood cell velocity suggesting upstream effects (1066). Other investigators have previously reported no effect of iberiotoxin on resting retinal arteriolar diameter in Wistar rats (1030).…”

Section: Bkca Channelsmentioning

confidence: 99%

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

270

347

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Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes.

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Section: Bkca Channelsmentioning

confidence: 99%

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

270

347

View full text Add to dashboard Cite

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“…In isolated rat retinal arterioles, addition of ATP triggers a robust constriction of the vessels 36 , while in the presence of an intact neuropile, the vessels dilate 37 . Therefore, wherever possible, we usually try to validate key findings from our isolated arteriole preparations using ex vivo retinal whole-mounts and in vivo measurements of vessel diameter and blood flow 16 37 . Of note, new methods have recently emerged for studying small arterioles and capillaries in whole perfused porcine retinas ex vivo 38 39 .…”

Section: Discussionmentioning

confidence: 99%

“…These vessels form the main site of vascular resistance within the retinal circulation and therefore play an important role in the local control of retinal blood flow. Retinal arterioles regulate capillary blood flow in the retina by dilating or constricting their luminal diameter, mediated by changes in vascular smooth muscle contractility 10 15 16 . Understanding the molecular mechanisms through which retinal arterioles regulate retinal perfusion therefore requires preparations where the arteriolar smooth muscle cells can be accessed and studied in conditions as close to physiological as possible.…”

Section: Introductionmentioning

confidence: 99%

Isolation of Retinal Arterioles for Ex Vivo Cell Physiology Studies

Curtis

McLaughlin

O’Hare

et al. 2018

JoVE

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The retina is a highly metabolically active tissue that requires a substantial blood supply. The retinal circulation supports the inner retina, while the choroidal vessels supply the photoreceptors. Alterations in retinal perfusion contribute to numerous sight-threatening disorders, including diabetic retinopathy, glaucoma and retinal branch vein occlusions. Understanding the molecular mechanisms involved in the control of blood flow through the retina and how these are altered during ocular disease could lead to the identification of new targets for the treatment of these conditions. Retinal arterioles are the main resistance vessels of the retina, and consequently, play a key role in regulating retinal hemodynamics through changes in luminal diameter. In recent years, we have developed methods for isolating arterioles from the rat retina which are suitable for a wide range of applications including cell physiology studies. This preparation has already begun to yield new insights into how blood flow is controlled in the retina and has allowed us to identify some of the key changes that occur during ocular disease. In this article, we describe methods for the isolation of rat retinal arterioles and include protocols for their use in patch-clamp electrophysiology, calcium imaging and pressure myography studies. These vessels are also amenable for use in PCR-, western blotting- and immunohistochemistry-based studies.

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“…The standard inhibitor for BK channels is iberiotoxin whose high price and membrane impermeability makes its use less than ideal for studies in organ models or whole animals. The higher membrane permeability, potency and efficacy of penitrem A may recommend this IDT as a good alternative to iberiotoxin for studying BK channels in vitro and in vivo (Stewart et al 2012; Asano et al 2012; Kyle et al 2013; Needham et al 2014). …”

Section: Future Perspectivesmentioning

confidence: 99%

Tremorgenic and neurotoxic paspaline-derived indole-diterpenes: biosynthetic diversity, threats and applications

Kozák

Szilágyi

Tóth

et al. 2019

Appl Microbiol Biotechnol

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Indole-diterpenes (IDTs) such as the aflatrems, janthitrems, lolitrems, paspalitrems, penitrems, shearinines, sulpinines, and terpendoles are biogenetically related but structurally varied tremorgenic and neurotoxic mycotoxins produced by fungi. All these metabolites derive from the biosynthetic intermediate paspaline, a frequently occurring IDT on its own right. In this comprehensive review, we highlight the similarities and differences of the IDT biosynthetic pathways that lead to the generation of the main paspaline-derived IDT subgroups. We survey the taxonomic distribution and the regulation of IDT production in various fungi and compare the organization of the known IDT biosynthetic gene clusters. A detailed assessment of the highly diverse biological activities of these mycotoxins leads us to emphasize the significant losses that paspaline-derived IDTs cause in agriculture, and compels us to warn about the various hazards they represent towards human and livestock health. Conversely, we also describe the potential utility of these versatile molecules as lead compounds for pharmaceutical drug discovery, and examine the prospects for their industrial scale manufacture in genetically manipulated IDT producers or domesticated host microorganisms in synthetic biological production systems.

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The Role of K⁺and Cl⁻Channels in the Regulation of Retinal Arteriolar Tone and Blood Flow

Cited by 11 publications

References 50 publications

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Isolation of Retinal Arterioles for <em>Ex Vivo</em> Cell Physiology Studies

Tremorgenic and neurotoxic paspaline-derived indole-diterpenes: biosynthetic diversity, threats and applications

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