Ca2+-induced uncoupling of Aplysia bag cell neurons

J Neurophysiol. 2015 Feb 1;113(3):808-21. doi: 10.1152/jn.00603.2014. Epub 2014 Nov 19.

Abstract

Electrical transmission is a dynamically regulated form of communication and key to synchronizing neuronal activity. The bag cell neurons of Aplysia are a group of electrically coupled neuroendocrine cells that initiate ovulation by secreting egg-laying hormone during a prolonged period of synchronous firing called the afterdischarge. Accompanying the afterdischarge is an increase in intracellular Ca2+ and the activation of protein kinase C (PKC). We used whole cell recording from paired cultured bag cell neurons to demonstrate that electrical coupling is regulated by both Ca2+ and PKC. Elevating Ca2+ with a train of voltage steps, mimicking the onset of the afterdischarge, decreased junctional current for up to 30 min. Inhibition was most effective when Ca2+ entry occurred in both neurons. Depletion of Ca2+ from the mitochondria, but not the endoplasmic reticulum, also attenuated the electrical synapse. Buffering Ca2+ with high intracellular EGTA or inhibiting calmodulin kinase prevented uncoupling. Furthermore, activating PKC produced a small but clear decrease in junctional current, while triggering both Ca2+ influx and PKC inhibited the electrical synapse to a greater extent than Ca2+ alone. Finally, the amplitude and time course of the postsynaptic electrotonic response were attenuated after Ca2+ influx. A mathematical model of electrically connected neurons showed that excessive coupling reduced recruitment of the cells to fire, whereas less coupling led to spiking of essentially all neurons. Thus a decrease in electrical synapses could promote the afterdischarge by ensuring prompt recovery of electrotonic potentials or making the neurons more responsive to current spreading through the network.

Keywords: calcium; electrical coupling; junctional current; neuroendocrine cell; protein kinase C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials*
  • Animals
  • Aplysia
  • Calcium / metabolism*
  • Calcium Signaling*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors
  • Electrical Synapses / metabolism
  • Electrical Synapses / physiology
  • Endoplasmic Reticulum / metabolism
  • Mitochondria / metabolism
  • Models, Neurological
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology*
  • Protein Kinase C / antagonists & inhibitors
  • Synaptic Transmission

Substances

  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium