Myoendothelial junctions in human brain arterioles.

Aydın, Faruk; Rosenblum, William I.; Povlishock, John T.

doi:10.1161/01.str.22.12.1592

Cited by 40 publications

(23 citation statements)

References 9 publications

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“…In this branch of the middle cerebral artery, interendothelial cell and intersmooth-muscle cell gap junctions could be observed, and in addition myoendothelial gap junctions were present suggesting that both homo-and heterocellular coupling exists between the different cell types; these findings are similar to those described in human cerebral arteries. 23 Because both IK Ca and SK Ca were expressed in the endothelium, and SLIGRL stimulates an endothelium-dependent response through a receptor coupled by G q/11 to rises in intracellular Ca 2ϩ , the likely explanation is that endothelial cell hyperpolarization may be transmitted to the muscle layers through myoendothelial gap junctions. However, it appears that when considering nonnuclear staining, both the SK2 and SK3 channels are very diffuse within the endothelium, suggesting low levels of expression.…”

Section: Discussionmentioning

confidence: 99%

Evidence for Involvement of Both IK _Ca and SK _Ca Channels in Hyperpolarizing Responses of the Rat Middle Cerebral Artery

McNeish

Sandow

Neylon

et al. 2006

Stroke

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Background and Purpose-Endothelium-derived hyperpolarizing factor responses in the rat middle cerebral artery are blocked by inhibiting IK Ca channels alone, contrasting with peripheral vessels where block of both IK Ca and SK Ca is required. As the contribution of IK Ca and SK Ca to endothelium-dependent hyperpolarization differs in peripheral arteries, depending on the level of arterial constriction, we investigated the possibility that SK Ca might contribute to equivalent hyperpolarization in cerebral arteries under certain conditions. Methods-Rat middle cerebral arteries (Ϸ175 m) were mounted in a wire myograph. The effect of K Ca channel blockers on endothelium-dependent responses to the protease-activated receptor 2 agonist, SLIGRL (20 mol/L), were then assessed as simultaneous changes in tension and membrane potential. These data were correlated with the distribution of arterial K Ca channels revealed with immunohistochemistry. Results-SLIGRL hyperpolarized and relaxed cerebral arteries undergoing variable levels of stretch-induced tone. The relaxation was unaffected by specific inhibitors of IK Ca (TRAM-34, 1 mol/L) or SK Ca (apamin, 50 nmol/L) alone or in combination. In contrast, the associated smooth-muscle hyperpolarization was inhibited, but only with these blockers in combination. Blocking nitric oxide synthase (NOS) or guanylyl cyclase evoked smooth-muscle depolarization and constriction, with both hyperpolarization and relaxation to SLIGRL being abolished by TRAM-34 alone, whereas apamin had no effect. Immunolabeling showed SK Ca and IK Ca within the endothelium. Conclusions-In the absence of NO, IK Ca underpins endothelium-dependent hyperpolarization and relaxation in cerebral arteries. However, when NOS is active SK Ca contributes to hyperpolarization, whatever the extent of background contraction. These changes may have relevance in vascular disease states where NO release is compromised and when the levels of SK Ca expression may be altered.

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Section: Discussionmentioning

confidence: 99%

Evidence for Involvement of Both IK _Ca and SK _Ca Channels in Hyperpolarizing Responses of the Rat Middle Cerebral Artery

McNeish

Sandow

Neylon

et al. 2006

Stroke

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“…5A). This finding suggest that myoendothelial gap junctions, which have been demonstrated to be present in resistance arteries and arterioles from different vascular beds (2,14,18,28), allow intercellular electrical coupling between endothelial and smooth muscle cells (10,13,14,20,39,40). Recent studies also demonstrated inhibition of ACh-induced, EDHF-type dilations in rabbit iliac (32) and mesentery arteries (9) and perfused murine hindlimb vessels (8) with structurally different gap junction inhibitors.…”

Section: Discussionmentioning

confidence: 96%

Increases in endothelial Ca²⁺activate K_Cachannels and elicit EDHF-type arteriolar dilation via gap junctions

Ungvári

Csiszár

Koller

2002

American Journal of Physiology-Heart and Circulatory Physiology

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] i ). However, recent studies revealed that in the endothelium of skeletal muscle arterioles, vessels that contribute importantly to the development of peripheral resistance, nitric oxide (NO) synthesis is activated by increases in shear stress without substantial increases in endothelial [Ca 2ϩ ] i , most likely by activation of Ca 2ϩ -independent tyrosine kinase pathways (35).In contrast, arteriolar dilations to agonists that act on endothelial receptors, such as acetylcholine (ACh), are associated with significant increases in endothelial [Ca 2ϩ ] i (7,23,34). Interestingly, in the microcirculation, in contrast to large vessels, a major part of AChinduced dilation is insensitive to the inhibition of NO synthase and cyclooxygenase. Pathways associated with NO-and prostaglandin-independent mediation involve smooth muscle hyperpolarization (3,7,14,34); therefore, it is termed endothelium-derived hyperpolarizing factor (EDHF)-type dilation. Despite its profound effect on arteriolar myogenic tone, the intra-and intercellular pathways for EDHF-type signal transduction are not well understood.Skeletal muscle arterioles are known to develop significant myogenic tone in response to intraluminal pressure, which depends on pressure-induced increases in smooth muscle [Ca 2ϩ ] i due to an influx of Ca 2ϩ through voltage-operated Ca 2ϩ channels (VOC) (33). Recently, we (34) demonstrated that EDHF-type arteriolar dilation to ACh is elicited by a decrease in smooth muscle [Ca 2ϩ ] i due to a hyperpolarization-dependent closure of VOC. However, the role of increases in endothelial [Ca 2ϩ ] i and the nature of coupling between endothelial activation and hyperpolarizationinduced decreases in smooth muscle [Ca 2ϩ ] i in EDHFtype arteriolar dilation remained to be resolved.From previous studies, we hypothesized that agonist-induced increases in arteriolar endothelial [Ca 2ϩ ] i elicit opening of endothelial Ca 2ϩ -activated K ϩ (K Ca ) channels, and the consequent hyperpolarization (11, 40) is conducted to the smooth muscle, likely via gap junctions (13,14,28,40) eliciting decreases in smooth muscle [Ca 2ϩ ] i and arteriolar dilations. To demonstrate that this hypothetic pathway is responsible for signal transduction of EDHF-type dilation of skeletal muscle arterioles, we measured simultaneous changes in endothelial [Ca 2ϩ ] i and diameter and characterized the role of endothelial K Ca channels

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“…Regional variation in the distribution of MEGJs, as found here in the RFA and in mesenteric arteries [31] could further add to the problem of detecting MEGJs using random sections. Indeed, the identification of MEGJs in studies employing random sections is limited to the carotid artery of the rabbit [39] and cerebral arterioles of humans [40]. However, through serial section electron microscopy these small junctions have been identified in numerous arteries of the rat and mouse, correlating well with their involvement in vascular function [28,29,31,41].…”

Section: Discussionmentioning

confidence: 99%

Expression of homocellular and heterocellular gap junctions in hamster arterioles and feed arteries

Sandow

2003

Cardiovascular Research

109

129

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Myoendothelial junctions in human brain arterioles.

Abstract: Background: The purpose of this work was to determine whether myoendothelial junctions were present in human brains.

Cited by 40 publications

References 9 publications

Evidence for Involvement of Both IK _Ca and SK _Ca Channels in Hyperpolarizing Responses of the Rat Middle Cerebral Artery

Evidence for Involvement of Both IK _Ca and SK _Ca Channels in Hyperpolarizing Responses of the Rat Middle Cerebral Artery

Increases in endothelial Ca²⁺activate K_Cachannels and elicit EDHF-type arteriolar dilation via gap junctions

Expression of homocellular and heterocellular gap junctions in hamster arterioles and feed arteries

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Myoendothelial junctions in human brain arterioles.

Abstract: Background: The purpose of this work was to determine whether myoendothelial junctions were present in human brains.

Cited by 40 publications

References 9 publications

Evidence for Involvement of Both IK Ca and SK Ca Channels in Hyperpolarizing Responses of the Rat Middle Cerebral Artery

Evidence for Involvement of Both IK Ca and SK Ca Channels in Hyperpolarizing Responses of the Rat Middle Cerebral Artery

Increases in endothelial Ca2+activate KCachannels and elicit EDHF-type arteriolar dilation via gap junctions

Expression of homocellular and heterocellular gap junctions in hamster arterioles and feed arteries

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Evidence for Involvement of Both IK _Ca and SK _Ca Channels in Hyperpolarizing Responses of the Rat Middle Cerebral Artery

Evidence for Involvement of Both IK _Ca and SK _Ca Channels in Hyperpolarizing Responses of the Rat Middle Cerebral Artery

Increases in endothelial Ca²⁺activate K_Cachannels and elicit EDHF-type arteriolar dilation via gap junctions