Gap Junction Channels Exhibit Connexin-specific Permeability to Cyclic Nucleotides

Kanaporis, Giedrius; Meşe, Gülistan; Valiuniene, Laima; White, Thomas W.; Brink, Peter R.; Valiūnas, Virginijus

doi:10.1083/jcb1812oia8

Cited by 26 publications

(39 citation statements)

References 42 publications

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“…We favor the notion that differential permeability of intercellular channels may play a more important role, as connexin-dependent differences in small molecule permeability have been observed in several studies (Harris 2007). For example, Cx43 channel permeability to cAMP is approximately three times higher than Cx26 and approximately five times higher than Cx40 (Kanaporis et al 2008), providing a conceptual framework for the observed differences in knockin phenotypes (Harris 2008).…”

Section: Gap Junctions In the Ocular Lensmentioning

confidence: 87%

Gap Junctions

Goodenough¹,

Paul²

2009

Cold Spring Harbor Perspectives in Biology

557

440

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Section: Gap Junctions In the Ocular Lensmentioning

confidence: 87%

Gap Junctions

Goodenough¹,

Paul²

2009

Cold Spring Harbor Perspectives in Biology

557

440

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“…1). However, connexin 43 (Cx43) is well recognized to form a major component of the PE-NPE gap junctions in this tissue (4,13,14,50), and cAMP has generally been found to increase or not affect Cx43 gap junctional communication in other preparations (33,35,51).…”

mentioning

confidence: 98%

Regulation of gap junction coupling in bovine ciliary epithelium

Wang

Wai

Valiūnas

et al. 2010

American Journal of Physiology-Cell Physiology

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Aqueous humor is formed by fluid transfer from the ciliary stroma sequentially across the pigmented ciliary epithelial (PE) cells, gap junctions, and nonpigmented ciliary epithelial (NPE) cells. Which connexins (Cx) contribute to PE-NPE gap junctional formation appears species specific. We tested whether small interfering RNA (siRNA) against Cx43 (siCx43) affects bovine PE-NPE communication and whether cAMP affects communication. Native bovine ciliary epithelial cells were studied by dual-cell patch clamping, Lucifer Yellow (LY) transfer, quantitative polymerase chain reaction with reverse transcription (qRT-PCR), and Western immunoblot. qRT-PCR revealed at least 100-fold greater expression for Cx43 than Cx40. siCx43 knocked down target mRNA expression by 55 ± 7% after 24 h, compared with nontargeting control siRNA (NTC1) transfection. After 48 h, siCx43 reduced Cx43 protein expression and LY transfer. The ratio of fluorescence intensity (Rf) in recipient to donor cell was 0.47 ± 0.09 ( n = 11) 10 min after whole cell patch formation in couplets transfected with NTC1. siCx43 decreased Rf by ∼60% to 0.20 ± 0.07 ( n = 13, P < 0.02). Dibutyryl-cAMP (500 μM) also reduced LY dye transfer by ∼60%, reducing Rf from 0.41 ± 0.05 ( n = 15) to 0.17 ± 0.05 ( n = 20) after 10 min. Junctional currents were lowered by ∼50% ( n = 6) after 10-min perfusion with 500 μM dibutyryl-cAMP ( n = 6); thereafter, heptanol abolished the currents ( n = 5). Preincubation with the PKA inhibitor H-89 (2 μM) prevented cAMP-triggered current reduction ( n = 6). We conclude that 1) Cx43, but not Cx40, is a major functional component of bovine PE-NPE gap junctions; and 2) under certain conditions, cAMP may act through PKA to inhibit bovine PE-NPE gap junctional communication.

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“…(18) and Cx43 has been described as more permeable to cAMP than Cx40 or Cx26 (25). The rapid diffusion of cAMP from cell to cell through Cx43 but not Cx40 or 26 would increase this nucleotide sufficiently to overcome the extremely effective phosphodieterase degradation and to trigger relevant cellular functions (25).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the Cxs associated in a given connexon may be homomeric or heteromeric, and equivalent or distinct connexons can dock to form homotypic or heterotypic GJ. Thus, a wide variety of GJ can exist, with different attributes in terms of their permeability to low-molecular-weight substances such as ATP, cAMP, IP 3 , or several dyes (25), justifying the need to identify the Cxs present in any given tissue. Several studies described the presence of Cx43, Cx40, and Cx37 in the bladder of different animal species, including humans, Cx43 being the most abundant (22,34,35,37).…”

mentioning

confidence: 99%

Direct coupling through gap junctions is not involved in urethral neurotransmission

Sancho

Triguero

Garcia-Pascual

2011

American Journal of Physiology-Renal Physiology

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cells of Cajal (ICC) are believed to participate in urethral neurotransmission and it was proposed that direct coupling of ICC and smooth muscle cells (SMC) through gap junctions (GJ) is involved, although this still remains unclear. Hence, we investigated the distribution of different connexins (Cx 43, Cx40, and Cx37) in the sheep and rat urethra, as well as their possible role in neurotransmission. Conventional PCR confirmed that three Cxs are expressed in the urethra. Moreover, both Cx43 and Cx37-immunoreactivity (-ir) were present in SMC, ICC, and the urothelium, although Cx37-ir was significantly weaker and Cx40-ir was limited to the endothelium. While these results indicate that GJ intercellular communication could occur between SMC and ICC, neither the contractile (noradrenergic) nor the relaxant (nitrergic) responses of the rat and sheep urethra to electrical field stimulation were significantly modified by two different GJ inhibitors: 18␣-glycyrrhetinic acid and a cocktail of Cx mimetic peptides ( Cx43 Gap 26, Cx37, Cx43 Gap 27, and Cx40 Gap 27). By contrast, contractions induced by high K ϩ were effectively reduced by both blockers, evidence that they effectively inhibit intercellular communication. These results indicate that GJ are not implicated in urethral neurotransmission, although the question of whether ICC modulate neurotransmission through some other mechanism remains to be determined.interstitial cells of Cajal; connexin; nitric oxide; norepinephrine URINARY CONTINENCE IS MAINTAINED at rest by a high spontaneous urethral tone, which is augmented by neurally released norepinephrine (NE). This high tone is abruptly lost during micturition by the release of nitric oxide (NO) from the nitrergic nerve network (reviewed in Ref. 1). Several investigations in the last decade led to the suggestion that the neurotransmission processes in the urethra are mediated by interstitial cells of Cajal (ICC) (15, 42, 43), similar to that described in the gastrointestinal tract (3, 5). In the lower urinary tract, it is now accepted the presence of a population of branched noncontractile cells with ultrastructural characteristics similar to those of the gut (41), which are ICC following the nomenclature guidelines approved in the Fifth International Symposium on Interstitial Cells of Cajal, Ireland, 2007. However, studies concerning their role in the urinary tract are scarce. In the urethra, the first description of vimentin-positive cells that accumulated cGMP immunoreactivity upon addition of NO donors, and with a remarkable resemblance to ICC of the intestine, was made by Smet et al. (45). Extensive studies using isolated rabbit ICC revealed the ionic mechanisms that are behind their proposed pacemaker role and these mechanisms are very similar to the activity of ICC seen in the gut (see Ref. 44 for a review). Furthermore, the presence of close contacts between ICC and nitrergic nerves in the urethra from several species has been described (15, 45), suggesting a functional relationship between them. This is ...

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Gap Junction Channels Exhibit Connexin-specific Permeability to Cyclic Nucleotides

Cited by 26 publications

References 42 publications

Gap Junctions

Gap Junctions

Regulation of gap junction coupling in bovine ciliary epithelium

Direct coupling through gap junctions is not involved in urethral neurotransmission

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