Article

Localization of heterotypic gap junctions composed of connexin45 and connexin36 in the rod pathway of the mouse retina

Department of Neurobiology, University of Oldenburg, D-26111 Oldenburg, Germany.
European Journal of Neuroscience (Impact Factor: 3.67). 10/2006; 24(6):1675-86. DOI: 10.1111/j.1460-9568.2006.05052.x
Source: PubMed

ABSTRACT The primary rod pathway in mammals contains gap junctions between AII amacrine cells and ON cone bipolar cells which relay the rod signal into the cone pathway under scotopic conditions. Two gap junctional proteins, connexin36 (Cx36) and connexin45 (Cx45), appear to play a pivotal role in this pathway because lack of either protein leads to an impairment of visual transmission under scotopic conditions. To investigate whether these connexins form heterotypic gap junctions between ON cone bipolar and AII amacrine cells, we used newly developed Cx45 antibodies and studied the cellular and subcellular distribution of this protein in the mouse retina. Specificity of the Cx45 antibodies was determined, among others, by Western blot and immunostaining of mouse heart, where Cx45 is abundantly expressed. In mouse retina, Cx45 immunosignals were detected in both plexiform layers and the ganglion cell layer. Double staining for Cx45 and Cx36 revealed a partial overlap in the punctate patterns in the ON sublamina of the inner plexiform layer of the retina. We quantified the distributions of these two connexins in the ON sublamina, and detected 30% of the Cx45 signals to be co-localized with or in close apposition to Cx36 signals. Combining immunostaining and intracellular dye injection revealed an overlap or tight association of Cx36 and Cx45 signals on the terminals of injected AII amacrine and two types of ON cone bipolar cells. Our results provide direct evidence for heterotypic gap junctions composed of Cx36 and Cx45 between AII amacrine and certain types of ON cone bipolar cells.

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    • "e connexon embedded in AII cell plasma membrane ( Feigenspan et al . , 2001 ; Güldenagel et al . , 2001 ; Mills et al . , 2001 ; Deans et al . , 2002 ) . There has been a debate , however , over the connexin subunit that forms ON cone bipolar cell connexons . While most studies detected Cx45 in bipolar cell hemichannels ( Maxeiner et al . , 2005 ; Dedek et al . , 2006 ; Hilgen et al . , 2011 ) , there is evidence for the presence of Cx36 as well ( Han and Massey , 2005 ) . This apparent inconsistency seems resolved by the finding that either Cx36 or Cx45 could contribute to ON bipolar cell connexons in a bi - polar cell type specific manner ( Lin et al . , 2005 ) . This implies that some of these cont"
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    • "Initial studies suggested that DA does not modulate AII–ON cone bipolar tracer coupling (Mills & Massey, 1995), which appears to be mediated by heteromeric Cx36/Cx45 gap junctions (Han & Massey, 2005; Maxeiner et al., 2005; Dedek et al., 2006 "
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    • "In adult retinas, Cx45 is expressed in bipolar cells (BCs), where it forms a part of the gap junction between AII amacrine cells and cone BCs (Han and Massey, 2005; Lin et al., 2005; Maxeiner et al., 2005; Dedek et al., 2006). It is also expressed in amacrine cells (Maxeiner et al., 2005; Dedek et al., 2006) and RGCs (Schubert et al., 2005a; for review, see Bloomfield and Völgyi, 2009). Cx45 antibodies produce strong labeling of mouse retinas from P1 to adulthood, and Cx45 mRNA levels are high at P1 and slowly decrease until adulthood (Kihara et al., 2006), similar to connexins that are transiently expressed in developing spinal cord (Chang et al., 1999). "
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