Novel method for measuring junctional proton permeation in isolated ventricular myocyte cell pairs

Swietach, Pawel; Vaughan‐Jones, Richard D.

doi:10.1152/ajpheart.00528.2004

Cited by 9 publications

(16 citation statements)

References 46 publications

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“…The regional intracellular alkalosis evoked by local NH 3 influx 25,26 induces H ϩ flux across the junction, which stabilizes within 30 seconds. 26 This produces a standing longitudinal H ϩ i gradient for the duration of dual microperfusion.…”

Section: Inducing Steady-state Junctional H ؉ Fluxmentioning

confidence: 99%

“…26 This produces a standing longitudinal H ϩ i gradient for the duration of dual microperfusion. The rate-limiting H ϩ flux results in a step-junctional H ϩ discontinuity (Figure 2Aii) that can be analyzed 26 to give a measure of P mob , using the steady-state boundary condition:…”

Section: Inducing Steady-state Junctional H ؉ Fluxmentioning

confidence: 99%

“…We also measured P mob under steady-state pH i conditions, using a different technique. One end of a ventricular cell pair (this time, from a guinea pig rather than rat heart) was exposed to Hepes-buffered solution containing 30 mmol/L NH 4 Cl to elevate pH i locally 25,26 ( Figure 2Ai). Within Ϸ30 seconds, this establishes an intracellular H ϩ gradient along the cell pair, which drives transjunctional H ϩ flux on the mobile buffer shuttle.…”

Section: Steady-state Ph I Sensitivity Of Junctional H ؉ Permeabilitymentioning

confidence: 99%

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H ⁺ Ion Activation and Inactivation of the Ventricular Gap Junction

Swietach

Rossini

Spitzer³

et al. 2007

Circulation Research

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Abstract-Hϩ ions are powerful modulators of cardiac function, liberated during metabolic activity. Among their physiological effects is a chemical gating of cell-to-cell communication, caused by H ϩ -mediated closure of connexin (Cx) channels at gap junctions. This protects surrounding tissue from the damaging effects of local intracellular acidosis. Cx proteins (largely Cx-43 in ventricle) form multimeric pores between cells, permitting translocation of ions and other solutes up to Ϸ1 kDa. The channels are essential for electrical and metabolic coordination of a tissue. Here we demonstrate that, contrary to expectation, H ϩ ions can induce an increase of gap-junctional permeability. This occurs during modest intracellular acid loads in myocyte pairs isolated from mammalian ventricle. We show that the increase in permeability allows a local rise of [H ϩ

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Section: Inducing Steady-state Junctional H ؉ Fluxmentioning

confidence: 99%

Section: Inducing Steady-state Junctional H ؉ Fluxmentioning

confidence: 99%

Section: Steady-state Ph I Sensitivity Of Junctional H ؉ Permeabilitymentioning

confidence: 99%

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H ⁺ Ion Activation and Inactivation of the Ventricular Gap Junction

Swietach

Rossini

Spitzer³

et al. 2007

Circulation Research

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“…IP3 (Romanello and D'Andrea P, 2001) 1a 1b 2 mobile pH buffers (Swietach and Vaughan-Jones, 2004) 1a 57…”

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confidence: 99%

“…43h (Kam et al, 1998) 3f 43h (Romanello and D'Andrea P, 2001) 3a 3c 3e 43j (Venance et al, 1997) 1a 1b 2 5 43j (Paemeleire et al, 2000) 1b 2 43j (Romanello and D'Andrea P, 2001) 1a 1b 2 32j > 43j > 26j 1b 2 (normalized by Mn spread, not junctional conductance) mobile pH buffers 43j (Swietach and Vaughan-Jones, 2004) 1a 57 NAD+ 43h (Bruzzone et al, 2001a;Bruzzone et al, 2001a) 3a 3b 3c 3f peptides ≤ 10mers 43j (Neijssen et al, 2005) 1a prostaglandin E2 43h (Jiang and Cherian, 2003;Cherian et al, 2005) 3a 3b 3c 3e RNA 12mer φ 26/32j (Valiunas et al, 2005) 1a 43j (Valiunas et al, 2005) 1a RNA 16mer 43j (Valiunas et al, 2005) 1a RNA 24mer 43j (Valiunas et al, 2005) 1a dsRNA 12mer φ 43j (Valiunas et al, 2005) 1a siRNA 22mer φ 26/32j (Valiunas et al, 2005) 1a 43j (Valiunas et al, 2005) 1a 5…”

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confidence: 99%

Connexin channel permeability to cytoplasmic molecules

Harris¹

2007

Progress in Biophysics and Molecular Biology

410

346

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Connexin channels are known to be permeable to a variety of cytoplasmic molecules. The first observation of second messenger junctional permeability, made ∼30 years ago, sparked broad interest in gap junction channels as mediators of intercellular molecular signaling. Since then, much has been learned about the diversity of connexin channels with regard to isoform diversity, tissue and developmental distribution, modes of channel regulation, assembly and expression, biochemical modification and permeability, all of which appear to be dynamically regulated. This information has expanded the potential roles of connexin channels in development, physiology and disease, and made their elucidation much more complex -30 years ago such an orchestra of junctional dynamics was unanticipated. Only recently, however, have investigators been able to directly address, in this more complex framework, the key issue: What specific biological molecules, second messengers and others, are able to permeate the various types of connexin channels, and how well? An important related issue, given the ever-growing list of connexin-related pathologies, is how these permeabilities are altered by disease-causing connexin mutations. Together, many studies show that a variety of cytoplasmic molecules can permeate the different types of connexin channels. A few studies reveal differences in permeation by different molecules through a particular type of connexin channel, and differences in permeation by a particular molecule through different types of connexin channels. This article describes and evaluates the various methods used to obtain these data, presents an annotated compilation of the results, and discusses the findings in the context of what can be inferred about mechanism of selectivity and potential relevance to signaling. The data strongly suggest that highly specific interactions take place between connexin pores and specific biological molecular permeants, and that those interactions determine which cytoplasmic molecules can permeate and how well. At this time, the nature of those interactions is unclear. One hopes that with more detailed permeability and structural information, the specific molecular mechanisms of the selectivity can be elucidated.

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