title: Differential regulation of action potential firing in adult murine thalamocortical neurons by Kv3.2, Kv1, and SK potassium and N-type calcium channels.
abstract: Sensory signals of widely differing dynamic range and intensity are transformed into a common firing rate code by thalamocortical neurons. While a great deal is known about the ionic currents, far less is known about the specific channel subtypes regulating thalamic firing rates. We hypothesized that different K(+) and Ca(2+) channel subtypes control different stimulus-response curve properties. To define the channels, we measured firing rate while pharmacologically or genetically modulating specific channel subtypes. Inhibiting Kv3.2 K(+) channels strongly suppressed maximum firing rate by impairing membrane potential repolarization, while playing no role in the firing response to threshold stimuli. By contrast, inhibiting Kv1 channels with alpha-dendrotoxin or maurotoxin strongly increased firing rates to threshold stimuli by reducing the membrane potential where action potentials fire (V(th)). Inhibiting SK Ca(2+)-activated K(+) channels with apamin robustly increased gain (slope of the stimulus-response curve) and maximum firing rate, with minimum effects on threshold responses. Inhibiting N-type Ca(2+) channels with omega-conotoxin GVIA or omega-conotoxin MVIIC partially mimicked apamin, while inhibiting L-type and P/Q-type Ca(2+) channels had small or no effects. EPSC-like current injections closely mimicked the results from tonic currents. Our results show that Kv3.2, Kv1, SK potassium and N-type calcium channels strongly regulate thalamic relay neuron sensory transmission and that each channel subtype controls a different stimulus-response curve property. Differential regulation of threshold, gain and maximum firing rate may help vary the stimulus-response properties across and within thalamic nuclei, normalize responses to diverse sensory inputs, and underlie sensory perception disorders.
authors.affiliation: Department of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kasten
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rudy
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Anderson
mesh_terms: D000200:Action Potentials; D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D054086:KATP Channels / Q000378:metabolism; D051656:KCNQ Potassium Channels / Q000378:metabolism; D007700:Kinetics; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012677:Sensation / Q000502:physiology*; D012684:Sensory Thresholds; D051637:Shaker Superfamily of Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051670:Shaw Potassium Channels / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; D054086:KATP Channels; D051656:KCNQ Potassium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D051637:Shaker Superfamily of Potassium Channels; D051670:Shaw Potassium Channels; D051640:Small-Conductance Calcium-Activated Potassium Channels; C498197:Cacna1g protein, mouse