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This Article Full Text Full Text (PDF) All Versions of this Article: 101/5/2339    most recent 00112.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Veruki, M. L. Articles by Hartveit, E. Search for Related Content PubMed PubMed Citation Articles by Veruki, M. L. Articles by Hartveit, E.

RESEARCH-ARTICLE

Meclofenamic Acid Blocks Electrical Synapses of Retinal AII Amacrine and ON-Cone Bipolar Cells

Department of Biomedicine, University of Bergen, Bergen, Norway

Submitted 6 February 2009; accepted in final form 9 March 2009

ABSTRACT

Gap junction channels constitute specialized intercellular contacts that can serve as electrical synapses. In the rod pathway of the retina, electrical synapses between AII amacrine cells express connexin 36 (Cx36) and electrical synapses between AII amacrines and ON-cone bipolar cells express Cx36 on the amacrine side and Cx36 or Cx45 on the bipolar side. For physiological investigations of the properties and functions of these electrical synapses, it is highly desirable to have access to potent pharmacological blockers with selective and reversible action. Here we use dual whole cell voltage-clamp recordings of pairs of AII amacrine cells and pairs of AII amacrine and ON-cone bipolar cells in rat retinal slices to directly measure the junctional conductance (G_j) between electrically coupled cells and to study the effect of the drug meclofenamic acid (MFA) on G_j. Consistent with previous tracer coupling studies, we found that MFA reversibly blocked the electrical synapse currents in a concentration-dependent manner, with complete block at 100 µM. Whereas MFA evoked a detectable decrease in G_j within minutes of application, the time to complete block of G_j was considerably longer, typically 20–40 min. After washout, G_j recovered to 20–90% of the control level, but the time to maximum recovery was typically >1 h. These results suggest that MFA can be a useful drug to investigate the physiological functions of electrical synapses in the rod pathway, but that the slow kinetics of block and reversal might compromise interpretation of the results and that explicit monitoring of G_j is desirable.