Evaluation of potassium ion as the endothelium‐derived hyperpolarizing factor (EDHF) in the bovine coronary artery

Nelli, Silvia; Wilson, William S.; Laidlaw, Hilary A; Llano, Andrea; Middleton, Susan Kay; Price, Andrew G; Martin, William J.

doi:10.1038/sj.bjp.0705329

Cited by 27 publications

(20 citation statements)

References 30 publications

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“…Edwards et al provided evidence that the targets of apamin and charybdotoxin are located on the endothelial cells, that potassium ions accumulate in the intercellular space between endothelial and smooth muscle cells, and that the potassium efflux associated with the activation of endothelial IK Ca and SK Ca channels produced hyperpolarization by activating both K IR and the Na + /K + pump on the smooth muscle cells. A role for the accumulation of K + ions in the intercellular space was then confirmed in many different arteries (145)(146)(147)(148)(149)(150)(151)(152). Nevertheless, this hypothesis has been highly controversial, possibly because the experimental conditions, and especially the presence or not of contractile agents, can markedly influence the contribution of K + ions in the overall mechanisms underlying endothelial-dependent hyperpolarizations.…”

Section: Beyond Endothelial Hyperpolarizationmentioning

confidence: 91%

Endothelium‐dependent hyperpolarizations: Past beliefs and present facts

2007

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Endothelium-dependent relaxations are attributed to the release of various factors, such as nitric oxide, carbon monoxide, reactive oxygen species, adenosine, peptides and arachidonic acid metabolites derived from the cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases pathways. The hyperpolarization of the smooth muscle cell can contribute to or be an integral part of the mechanisms underlying the relaxations elicited by virtually all these endothelial mediators. These endothelium-derived factors can activate different families of K(+) channels of the vascular smooth muscle. Other events associated with the hyperpolarization of both the endothelial and the vascular smooth muscle cells (endothelium-derived hyperpolarizing factor (EDHF)-mediated responses) contribute also to endothelium-dependent relaxations. These responses involve an increase in the intracellular Ca(2+) concentration of the endothelial cells followed by the opening of Ca(2+)-activated K(+) channels of small and intermediate conductance and the subsequent hyperpolarization of these cells. Then, the endothelium-dependent hyperpolarization of the underlying smooth muscle cells can be evoked by direct electrical coupling through myoendothelial junctions and/or the accumulation of K(+) ions in the intercellular space between the two cell types. These various mechanisms are not necessarily mutually exclusive and, depending on the vascular bed and the experimental conditions, can occur simultaneously or sequentially, or also may act synergistically.

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Section: Beyond Endothelial Hyperpolarizationmentioning

confidence: 91%

Endothelium‐dependent hyperpolarizations: Past beliefs and present facts

2007

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“…Since the original proposal that the diffusible EDHF in rat hepatic and mesenteric arteries was none other than the ionised K + ions that originated from activated endothelial cells [40], the hypothesis has received significant endorsement. Thus, K + signalling seems to play a key role not only in these rat vessels [36,43], but also in a variety of other bovine [97], human [20], murine [91], porcine [10] and rat [27] arteries. From a variety of methodological studies, the critical K IR channel is likely to be formed from a tetramer of K IR 2.1 α-subunits [17,39], while the Na + /K + -ATPase isoforms capable of responding to a raised [K + ] are those containing either the α2 or α3 subunits [12,39].…”

Section: Endothelial Cell-derived K + As An Edhfmentioning

confidence: 99%

Endothelium-derived hyperpolarising factors and associated pathways: a synopsis

Edwards

Félétou

Weston

2010

Pflugers Arch - Eur J Physiol

323

332

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The term endothelium-derived hyperpolarising factor (EDHF) was introduced in 1987 to describe the hypothetical factor responsible for myocyte hyperpolarisations not associated with nitric oxide (EDRF) or prostacyclin. Two broad categories of EDHF response exist. The classical EDHF pathway is blocked by apamin plus TRAM-34 but not by apamin plus iberiotoxin and is associated with endothelial cell hyperpolarisation. This follows an increase in intracellular [Ca(2+)] and the opening of endothelial SK(Ca) and IK(Ca) channels preferentially located in caveolae and in endothelial cell projections through the internal elastic lamina, respectively. In some vessels, endothelial hyperpolarisations are transmitted to myocytes through myoendothelial gap junctions without involving any EDHF. In others, the K(+) that effluxes through SK(Ca) activates myocytic and endothelial Ba(2+)-sensitive K(IR) channels leading to myocyte hyperpolarisation. K(+) effluxing through IK(Ca) activates ouabain-sensitive Na(+)/K(+)-ATPases generating further myocyte hyperpolarisation. For the classical pathway, the hyperpolarising "factor" involved is the K(+) that effluxes through endothelial K(Ca) channels. During vessel contraction, K(+) efflux through activated myocyte BK(Ca) channels generates intravascular K(+) clouds. These compromise activation of Na(+)/K(+)-ATPases and K(IR) channels by endothelium-derived K(+) and increase the importance of gap junctional electrical coupling in myocyte hyperpolarisations. The second category of EDHF pathway does not require endothelial hyperpolarisation. It involves the endothelial release of factors that include NO, HNO, H(2)O(2) and vasoactive peptides as well as prostacyclin and epoxyeicosatrienoic acids. These hyperpolarise myocytes by opening various populations of myocyte potassium channels, but predominantly BK(Ca) and/or K(ATP), which are sensitive to blockade by iberiotoxin or glibenclamide, respectively.

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“…Although the identity of EDHF has been the subject of considerable controversy [134], recent evidence suggests that EDHF is a K + ion, at least in hepatic, gastric, and cerebral arteries [14,75,85]. In addition, a number of reports have suggested that K + plays a role in the arterial response to EDHF [135][136][137], which involves the liberation of K + via endothelial Ca 2+ -activated K + channels with subsequently Kir2 channel activation, within the smooth muscle layer [84,89,138].…”

Section: Modulation Of Kir2 Channels By Edhf and Sodium Nitroprussidementioning

confidence: 98%

Physiological role of inward rectifier K+ channels in vascular smooth muscle cells

Park

Han

Earm

2008

Pflugers Arch - Eur J Physiol

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K(+) channels play indispensable roles in establishing the membrane potential and in regulating the contractile tone of arterial smooth muscle cells. There are four types of K(+) channels in arterial smooth muscle: voltage-dependent K(+) (K(V)), Ca(2+)-dependent K(+) (BK(Ca)), ATP-dependent K(+) (K(ATP)), and inward rectifier K(+) (Kir2) channels. Comparatively few physiological studies have focused on Kir2 channels because they are present only in certain small-diameter cerebral and submucosal arterioles and in coronary arterial smooth muscle. Here, we review the characteristics and regulation of Kir2 channels in vascular arterial smooth muscle. Current knowledge of the predominant Kir2 channel subtype is Kir2.1, not Kir2.2 and 2.3. Electrophysiological measurements to determine the current-voltage relationship in arterial smooth muscle revealed inward rectification with a single-channel conductance of 21 pS. Kir2 channels were found to influence the resting tone of cerebral and coronary arteries based on the fact that barium (Ba(2+)) induces the constriction of these arteries at resting tone. Kir2 channels are also highly responsive to vasoconstrictors and vasodilators. For example, the vasoconstrictors endothelin-1 and angiotensin II inhibit Kir2 channel function by activating protein kinase C (PKC), and the vasodilator adenosine stimulates Kir2 channel function by increasing the level of cAMP, which subsequently activates protein kinase A (PKA). Certain pathological conditions such as left ventricular hypertrophy are associated with a decrease in Kir2 channel expression. Although our understanding of the physiological role and regulation of Kir2 channels is incomplete, it is believed that Kir2 channels contribute to the control of vascular tone in small-diameter vessels via various intracellular signalling pathways that regulate cell membrane potential.

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Evaluation of potassium ion as the endothelium‐derived hyperpolarizing factor (EDHF) in the bovine coronary artery

Cited by 27 publications

References 30 publications

Endothelium‐dependent hyperpolarizations: Past beliefs and present facts

Endothelium‐dependent hyperpolarizations: Past beliefs and present facts

Endothelium-derived hyperpolarising factors and associated pathways: a synopsis

Physiological role of inward rectifier K+ channels in vascular smooth muscle cells

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