Connexin 37 is localized in renal epithelia and responds to changes in dietary salt intake

Stoessel, Adelina; Himmerkus, Nina; Bleich, Markus; Bachmann, S.; Theilig, Franziska

doi:10.1152/ajprenal.00295.2009

Cited by 39 publications

(28 citation statements)

References 35 publications

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“…These results suggest that -induced, BK-mediated K efflux has both P 2 -dependent and P 2 -independent components and -induced ATP release is dependent on K efflux. That K efflux is dependent on ATP efflux was revealed by application of carbenoxolone, an inhibitor of connexins and hemichannels (47). In C11, carbenoxolone inhibited 72% of the -induced K efflux and nearly all ATP release, suggesting dependence of K efflux on ATP extrusion via connexins.…”

Section: Discussionmentioning

confidence: 99%

Coupled ATP and potassium efflux from intercalated cells

Holtzclaw

Cornelius

Hatcher

et al. 2011

American Journal of Physiology-Renal Physiology

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Increased flow in the distal nephron induces K secretion through the large-conductance, calcium-activated K channel (BK), which is primarily expressed in intercalated cells (IC). Since flow also increases ATP release from IC, we hypothesized that purinergic signaling has a role in shear stress (τ; 10 dynes/cm(2)) -induced, BK-dependent, K efflux. We found that 10 μM ATP led to increased IC Ca concentration, which was significantly reduced in the presence of the P(2) receptor blocker suramin or calcium-free buffer. ATP also produced BK-dependent K efflux, and IC volume decrease. Suramin inhibited τ-induced K efflux, suggesting that K efflux is at least partially dependent on purinergic signaling. BK-β4 small interfering (si) RNA, but not nontarget siRNA, decreased ATP secretion and both ATP-dependent and τ-induced K efflux. Similarly, carbenoxolone (25 μM), which blocks connexins, putative ATP pathways, blocked τ-induced K efflux and ATP secretion. Compared with BK-β4(-/-) mice, wild-type mice with high distal flows exhibited significantly more urinary ATP excretion. These data demonstrate coupled electrochemical efflux between K and ATP as part of the mechanism for τ-induced ATP release in IC.

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Section: Discussionmentioning

confidence: 99%

Coupled ATP and potassium efflux from intercalated cells

Holtzclaw

Cornelius

Hatcher

et al. 2011

American Journal of Physiology-Renal Physiology

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“…In addition, Cx37 expression was noticed in intraglomerular capillaries, while expression of Cx43 was only minor [12,14,25]. Furthermore, Panx3 presence has been seen in these cells [17].…”

Section: Glomerular Endotheliummentioning

confidence: 95%

“…The role of other epithelial Cxs in tubular function is still unknown. However, rats treated with low-salt diet showed a significant increase in Cx37 levels in renal cortex, which may indicate a functional role for this Cx species in renal tubules [25]. In addition, a recent study from Hanner and collaborators demonstrated a major role for Panx1-based channels in ATP release.…”

Section: Gap Junctions and Tubular Functionmentioning

confidence: 96%

“…It is of interest that the expression pattern of these Cx species is cell type-specific. For instance, in cortical collecting ducts, Cx37 is expressed by principal cells basolaterally, whereas Cx30 in the same segment is restricted to intercalated cells at the luminal surface in the form of HCs [25,31]. A recent study showed Panx1 expression in several tubular segments, including proximal tubules, thin descending limbs and collecting ducts, along their apical cell membranes [19].…”

Section: Tubulesmentioning

confidence: 99%

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Functional roles of connexins and pannexins in the kidney

Abed

Kavvadas

Chadjichristos

2015

Cell. Mol. Life Sci.

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Kidneys are highly complex organs, playing a crucial role in human physiopathology, as they are implicated in vital processes, such as fluid filtration and vasomotor tone regulation. There is growing evidence that gap junctions are major determinants of renal physiopathology. It has been demonstrated that their expression or channel activity may vary depending on physiological and pathological situations within distinct renal compartments. While some studies have focused on the role of connexins in renal physiology, our knowledge regarding the functional relevance of pannexins is still very limited. In this paper, we provide an overview of the involvement of connexins, pannexins and their channels in various physiological processes related to different renal compartments.

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“…The abundance of phosphorylated NHE3 was increased in proximal tubule brush-border membrane fractions in response to a high sodium intake, which may have contributed to its redistribution within the microvilli (72). A high salt intake has been shown to alter the expression and/or activity of a number of signaling molecules in the thick ascending limb, including endothelial nitric oxide synthetase, cytochrome P-450 epoxygenase, cyclooxygenase-2, AMP-activated protein kinase, and connexin 37 (20,36,39,61,63,73). Whether these or other signaling pathways may contribute to the adaptive increase in NHE3 activity and HCO 3 Ϫ absorption caused by high sodium intake in the MTAL remains to be determined.…”

Section: Of Hcomentioning

confidence: 99%

High sodium intake increases HCO₃⁻absorption in medullary thick ascending limb through adaptations in basolateral and apical Na⁺/H⁺exchangers

Good

George²,

Watts³

2011

American Journal of Physiology-Renal Physiology

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A high sodium intake increases the capacity of the medullary thick ascending limb (MTAL) to absorb HCO(3)(-). Here, we examined the role of the apical NHE3 and basolateral NHE1 Na(+)/H(+) exchangers in this adaptation. MTALs from rats drinking H(2)O or 0.28 M NaCl for 5-7 days were perfused in vitro. High sodium intake increased HCO(3)(-) absorption rate by 60%. The increased HCO(3)(-) absorptive capacity was mediated by an increase in apical NHE3 activity. Inhibiting basolateral NHE1 with bath amiloride eliminated 60% of the adaptive increase in HCO(3)(-) absorption. Thus the majority of the increase in NHE3 activity was dependent on NHE1. A high sodium intake increased basolateral Na(+)/H(+) exchange activity by 89% in association with an increase in NHE1 expression. High sodium intake increased apical Na(+)/H(+) exchange activity by 30% under conditions in which basolateral Na(+)/H(+) exchange was inhibited but did not change NHE3 abundance. These results suggest that high sodium intake increases HCO(3)(-) absorptive capacity in the MTAL through 1) an adaptive increase in basolateral NHE1 activity that results secondarily in an increase in apical NHE3 activity; and 2) an adaptive increase in NHE3 activity, independent of NHE1 activity. These studies support a role for NHE1 in the long-term regulation of renal tubule function and suggest that the regulatory interaction whereby NHE1 enhances the activity of NHE3 in the MTAL plays a role in the chronic regulation of HCO(3)(-) absorption. The adaptive increases in Na(+)/H(+) exchange activity and HCO(3)(-) absorption in the MTAL may play a role in enabling the kidneys to regulate acid-base balance during changes in sodium and volume balance.

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Connexin 37 is localized in renal epithelia and responds to changes in dietary salt intake

Abstract: Stoessel A, Himmerkus N, Bleich M, Bachmann S, Theilig F. Connexin 37 is localized in renal epithelia and responds to changes in dietary salt intake.

Cited by 39 publications

References 35 publications

Coupled ATP and potassium efflux from intercalated cells

Coupled ATP and potassium efflux from intercalated cells

Functional roles of connexins and pannexins in the kidney

High sodium intake increases HCO₃⁻absorption in medullary thick ascending limb through adaptations in basolateral and apical Na⁺/H⁺exchangers

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Connexin 37 is localized in renal epithelia and responds to changes in dietary salt intake

Abstract: Stoessel A, Himmerkus N, Bleich M, Bachmann S, Theilig F. Connexin 37 is localized in renal epithelia and responds to changes in dietary salt intake.

Cited by 39 publications

References 35 publications

Coupled ATP and potassium efflux from intercalated cells

Coupled ATP and potassium efflux from intercalated cells

Functional roles of connexins and pannexins in the kidney

High sodium intake increases HCO3−absorption in medullary thick ascending limb through adaptations in basolateral and apical Na+/H+exchangers

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High sodium intake increases HCO₃⁻absorption in medullary thick ascending limb through adaptations in basolateral and apical Na⁺/H⁺exchangers