Persistent sodium currents in mesencephalic v neurons participate in burst generation and control of membrane excitability.
The functional and biophysical properties of a persistent sodium current (I(NaP)) previously proposed to participate in the generation of subthreshold oscillations and burst discharge in mesencephalic trigeminal sensory neurons (Mes V) were investigated in brain stem slices (rats, p7-p12) using whole cell patch-clamp methods. I(NaP) activated around -76 mV and peaked at -48 mV, with V1/2 of -58.7 mV. Ramp voltage-clamp protocols showed that I(NaP) undergoes time- as well as voltage-dependent inactivation and recovery from inactivation in the range of several seconds (tau(onset) = 2.04 s, tau(recov) = 2.21 s). Riluzole (< or =5 microM) substantially reduced I(NaP), membrane resonance, postinhibitory rebound (PIR), and subthreshold oscillations, and completely blocked bursting, but produced modest effects on the fast transient Na+ current (I(NaT)). Before complete cessation, burst cycle duration was increased substantially, while modest and inconsistent changes in burst duration were observed. The properties of the I(NaT) were obtained and revealed that the amplitude and voltage dependence of the resulting "window current" were not consistent with those of the observed I(NaP) recorded in the same neurons. This suggests an additional mechanism for the origin of I(NaP). A neuronal model was constructed using Hodgkin-Huxley parameters obtained experimentally for Na+ and K+ currents that simulated the experimentally observed membrane resonance, subthreshold oscillations, bursting, and PIR. Alterations in the model g(NaP) parameters indicate that I(NaP) is critical for control of subthreshold and suprathreshold Mes V neuron membrane excitability and burst generation.
Wu
Nanping
N
Department of Physiological Science, UCLA, 2859 Slichter Hall, Los Angeles, CA 90095, USA.
Enomoto
Akifumi
A
Tanaka
Susumu
S
Hsiao
Chie-Fang
CF
Nykamp
Duane Q
DQ
Izhikevich
Eugene
E
Chandler
Scott H
SH
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics / Q000379:methods; D002104:Cadmium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000528:radiation effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008636:Mesencephalon / Q000166:cytology*; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D011743:Pyrimidines; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D002104:Cadmium; C082246:ICI D2788; D013779:Tetrodotoxin; D019782:Riluzole