Sodium currents in mesencephalic trigeminal neurons from Nav1.6 null mice.
Previous studies using pharmacological methods suggest that subthreshold sodium currents are critical for rhythmical burst generation in mesencephalic trigeminal neurons (Mes V). In this study, we characterized transient (I(NaT)), persistent (I(N)(aP)), and resurgent (I(res)) sodium currents in Na(v)1.6-null mice (med mouse, Na(v)1.6(-/-)) lacking expression of the sodium channel gene Scn8a. We found that peak transient, persistent, and resurgent sodium currents from med (Na(v)1.6(-/-)) mice were reduced by 18, 39, and 76% relative to their wild-type (Na(v)1.6(+/+)) littermates, respectively. Current clamp recordings indicated that, in response to sinusoidal constant amplitude current (ZAP function), all neurons exhibited membrane resonance. However, Mes V neurons from med mice had reduced peak amplitudes in the impedance-frequency relationship (resonant Q-value) and attenuated subthreshold oscillations despite the similar passive membrane properties compared with wild-type littermates. The spike frequency-current relationship exhibited reduced instantaneous discharge frequencies and spike block at low stimulus currents and seldom showed maintained spike discharge throughout the stimulus in the majority of med neurons compared with wild-type neurons. Importantly, med neurons never exhibited maintained stimulus-induced rhythmical burst discharge unlike those of wild-type littermates. The data showed that subthreshold sodium currents are critical determinants of Mes V electrogenesis and burst generation and suggest a role for resurgent sodium currents in control of spike discharge.
Enomoto
Akifumi
A
Department of Physiological Science, University of California, Los Angeles, California 90095, USA.
Han
Juliette M
JM
Hsiao
Chie-Fang
CF
Chandler
Scott H
SH
D000818:Animals; D000831:Animals, Newborn; D004056:Differential Threshold / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D005583:Fourier Analysis; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000235:genetics* / Q000502:physiology; D008636:Mesencephalon / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011743:Pyrimidines / Q000494:pharmacology; D015222:Sodium Channels / Q000172:deficiency*; D014278:Trigeminal Nuclei / Q000502:physiology*
D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D011743:Pyrimidines; C491046:Scn8a protein, mouse; D015222:Sodium Channels; C034821:4-aminopyrimidine