title: Differential responses to ω-agatoxin IVA in murine frontal cortex and spinal cord derived neuronal networks.
abstract: ω-Agatoxin-IVA is a well known P/Q-type Ca(2+) channel blocker and has been shown to affect presynaptic Ca(2+) currents as well postsynaptic potentials. P/Q-type voltage gated Ca(2+) channels play a vital role in presynaptic neurotransmitter release and thus play a role in action potential generation. Monitoring spontaneous activity of neuronal networks on microelectrode arrays (MEAs) provides an important tool for examining this neurotoxin. Changes in extracellular action potentials are readily observed and are dependent on synaptic function. Given the efficacy of murine frontal cortex and spinal cord networks to detect neuroactive substances, we investigated the effects of ω-agatoxin on spontaneous action potential firing within these networks. We found that networks derived from spinal cord are more sensitive to the toxin than those from frontal cortex; a concentration of only 10nM produced statistically significant effects on activity from spinal cord networks whereas 50 nM was required to alter activity in frontal cortex networks. Furthermore, the effects of the toxin on frontal cortex are more complex as unit specific responses were observed. These manifested as either a decrease or increase in action potential firing rate which could be statistically separated as unique clusters. Administration of bicuculline, a GABAA inhibitor, isolated a single response to ω-agatoxin, which was characterized by a reduction in network activity. These data support the notion that the two clusters detected with ω-agatoxin exposure represent differential responses from excitatory and inhibitory neuronal populations.
authors.affiliation: Department of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, 4400 University Dr. MSN 2A1, Fairfax, VA 22030, USA. gknaack@masonlive.gmu.edu
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Knaack
authors.forename: Hamid
authors.initials: H
authors.lastname: Charkhkar
authors.forename: Franz W
authors.initials: FW
authors.lastname: Hamilton
authors.forename: Nathalia
authors.initials: N
authors.lastname: Peixoto
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: O'Shaughnessy
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Pancrazio
mesh_terms: D000200:Action Potentials; D000818:Animals; D002121:Calcium Channel Blockers / Q000633:toxicity*; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D051379:Mice; D009415:Nerve Net / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009433:Neural Inhibition / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020867:omega-Agatoxin IVA / Q000633:toxicity*
chemical_list: D002121:Calcium Channel Blockers; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D058787:GABA-A Receptor Antagonists; D020867:omega-Agatoxin IVA