The role of calmodulin and calcium calmodulin dependent protein kinase II (CamKII) in axo -axonal coupling

Bertina Michelle Scott, Purdue University


Modulation of the fast electrical transmission between neurons could lead to changes that affect learning processes. We are interested in the influence of modulated gap junction-mediated electrical synapses on the impulse activity in a network of nerve cells. CamKII, an important player in learning processes, can alter activity within a neuronal network; however, less is known about its role in modulating electrical synapses. The leech S cell network provides an excellent model to test whether a calmodulin (CAM)/CamKII pathway affects gap junctional communication between nerve cells. To determine the role of CAM/CamKII in intercellular communication, we used electrophysiological recordings of action potential latencies to assess the effects of neuronal activity and inhibition of CAM and CamKII on the propagation of nerve impulses through the network of S cells. Both neuronal activity and inhibition of CAM and CamKII caused gap junction-mediated axo-axonal uncoupling of S cells in a time dependent manner. A rapid activity-dependent decrease in coupling occurring within 3 seconds of nerve stimulation was greatly enhanced by calmodulin inhibition, but not by CamKII inhibition. A more profound axo-axonal uncoupling of S cells emerged 10 minutes after bath-application of CAM and CamKII inhibitors. The lack of effect of voltage gated Ca2+ channel inhibition and chelation of free intracellular Ca2+ on the action potential latencies indicated that short-term modulation of axo-axonal coupling by activity occurred in a Ca2+-independent manner. CamKII was shown to play a role in long-term maintenance of electrical coupling between nerve cells, whereas calmodulin contributed in both short- and long-term maintenance of the electrical coupling. It is speculated that the calmodulin/CamKII-dependent modulation of electrical synapses between neurons described in these studies may have a significant role in learning processes.




Sahley, Purdue University.

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