Calcium channel and glutamate receptor activities regulate actin organization in salamander retinal neurons

Intracellular Ca 2+ regulates a variety of neuronal functions, including neurotransmitter release, protein phosphorylation, gene expression and synaptic plasticity. In a variety of cell types, including neurons, Ca 2+ is involved in actin reorganization, resulting in either actin polymerization or depolymerization. Very little, however, is known about the relationship between Ca 2+ and the actin cytoskeleton organization in retinal neurons. We studied the effect of high‐K + ‐induced depolarization on F‐actin organization in salamander retina and found that Ca 2+ influx through voltage‐gated L‐type channels causes F‐actin disruption, as assessed by 53 ± 5% ( n = 23, P < 0.001) reduction in the intensity of staining with Alexa‐Fluor488‐phalloidin, a compound that permits visualization and quantification of polymerized actin. Calcium‐induced F‐actin depolymerization was attenuated in the presence of protein kinase C antagonists, chelerythrine or bis‐ indolylmaleimide hydrochloride (GF 109203X). In addition, phorbol 12‐myristate 13‐acetate (PMA), but not 4α‐PMA, mimicked the effect of Ca 2+ influx on F‐actin. Activation of ionotropic AMPA and NMDA glutamate receptors also caused a reduction in F‐actin. No effect on F‐actin was exerted by caffeine or thapsigargin, agents that stimulate Ca 2+ release from internal stores. In whole‐cell recording from a slice preparation, light‐evoked ‘off’ but not ‘on’ EPSCs in ‘on–off’ ganglion cells were reduced by 60 ± 8% ( n = 8, P < 0.01) by cytochalasin D. These data suggest that elevation of intracellular Ca 2+ during excitatory synaptic activity initiates a cascade for activity‐dependent actin remodelling, which in turn may serve as a feedback mechanism to attenuate excitotoxic Ca 2+ accumulation induced by synaptic depolarization.