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Rationale: Plakophilin-2 (PKP2) is an essential component of the cardiac desmosome. Recent data show that it interacts with other molecules of the intercalated disc. Separate studies show preferential localization of the voltage-gated sodium channel (Na V 1.5) to this region. Objective: To establish the association of PKP2 with sodium channels and its role(More)
AIMS Cell function requires formation of molecular clusters localized to discrete subdomains. The composition of these interactomes, and their spatial organization, cannot be discerned by conventional microscopy given the resolution constraints imposed by the diffraction limit of light (∼200-300 nm). Our aims were (i) Implement single-molecule imaging and(More)
RATIONALE The early description of the intercalated disc defined 3 structures, all of them involved in cell-cell communication: desmosomes, gap junctions, and adherens junctions. Current evidence demonstrates that molecules not involved in providing a physical continuum between cells also populate the intercalated disc. Key among them is the voltage-gated(More)
Connexins proteins associate with a variety of catalytic and non-catalytic molecules. Also, different domains of connexin can bind to each other, providing a mechanism for channel regulation. Here, we review some of these associations, placing particular emphasis on the intramolecular interactions that regulate Connexin43 (Cx43). We also describe some novel(More)
The regulation of junctional conductance (Gi) of the major cardiac (connexin43; Cx43) and liver (connexin32; Cx32) gap junction proteins by intracellular hydrogen ion concentration (pH; pHi), as well as well as that of a truncation mutant of Cx43 (M257) with 125 amino acids deleted from the COOH terminus, was characterized in pairs of Xenopus laevis oocytes(More)
Connexin43(Cx43) channels can be regulated by a variety of factors, including low pHi. Structure/function studies from this laboratory have demonstrated that pH gating follows a particle-receptor mechanism, similar to the "ball-and-chain" model of voltage-dependent inactivation of ion channels. The question whether the particle-receptor model is applicable(More)
The molecular mechanisms controlling pH-sensitivity of gap junctions formed of two different connexins are yet to be determined. We used a proton-sensitive fluorophore and electrophysiological techniques to correlate changes in intracellular pH (pHi) with electrical coupling between connexin-expressing Xenopus oocytes. The pH sensitivities of alpha 3(More)
The proton and Zn2+ effects on the human ether-a-go-go related gene (HERG) channels were studied after expression in Xenopus oocytes and stable transfection in the mammalian L929 cell line. Experiments were carried out using the two-electrode voltage clamp at room temperature (oocytes) or the whole-cell patch clamp technique at 35 degrees C (L929 cells). In(More)
BACKGROUND Sodium channel α-subunits in ventricular myocytes (VMs) segregate either to the intercalated disc or to lateral membranes, where they associate with region-specific molecules. OBJECTIVE To determine the functional properties of sodium channels as a function of their location in the cell. METHODS Local sodium currents were recorded from adult(More)
Immunohistochemical co-localization of distinct connexins (Cxs) in junctional areas suggests the formation of heteromultimeric channels. To determine the docking effects of the heterotypic combination of Cx43 and Cx45 on the voltage-gating properties of their channels, we transfected DNA encoding Cx43 or Cx45 into N2A neuroblastoma or HeLa cells. Using a(More)