title: Ca2+-induced uncoupling of Aplysia bag cell neurons.
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.
authors.affiliation: Department of Biomedical and Molecular Sciences, Physiology Graduate Program, Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Dargaei
authors.affiliation: Department of Biomedical and Molecular Sciences, Physiology Graduate Program, Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
authors.forename: Dominic
authors.initials: D
authors.lastname: Standage
authors.affiliation: Department of Biomedical and Molecular Sciences, Physiology Graduate Program, Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Groten
authors.affiliation: Department of Biomedical and Molecular Sciences, Physiology Graduate Program, Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Blohm
authors.affiliation: Department of Biomedical and Molecular Sciences, Physiology Graduate Program, Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada magoski@queensu.ca.
authors.forename: Neil S
authors.initials: NS
authors.lastname: Magoski
mesh_terms: D000200:Action Potentials; D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors; D054351:Electrical Synapses / Q000378:metabolism / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission
chemical_list: D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
keywords: calcium; electrical coupling; junctional current; neuroendocrine cell; protein kinase C