Submitted on February 6, 2009
Revised on March 9, 2009
Accepted on March 9, 2009
Meclofenamic acid blocks electrical synapses of retinal AII amacrine and ON-cone bipolar cells
Margaret Lin Veruki1 and Espen Hartveit1*
1 University of Bergen
* To whom correspondence should be addressed. E-mail: espen.hartveit{at}biomed.uib.no.
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 (Gj) between electrically coupled cells and to study the effect of the drug meclofenamic acid on Gj. Consistent with previous tracer coupling studies, we found that meclofenamic acid reversibly blocked the electrical synapse currents in a concentration-dependent manner, with complete block at 100 µM. While meclofenamic acid evoked a detectable decrease in Gj within minutes of application, the time to complete block of Gj was considerably longer, typically 20-40 min. After washout, Gj recovered to 20-90% of the control level, but the time to maximum recovery was typically >1 hour. These results suggest that meclofenamic acid 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 Gj is desirable.
