Sodium currents in medullary neurons isolated from the pre-Bötzinger complex region.
The pre-Bötzinger complex (preBötC) in the ventrolateral medulla contains interneurons important for respiratory rhythm generation. Voltage-dependent sodium channels mediate transient current (I(NaT)), underlying action potentials, and persistent current (I(NaP)), contributing to repetitive firing, pacemaker properties, and the amplification of synaptic inputs. Voltage-clamp studies of the biophysical properties of these sodium currents were conducted on acutely dissociated preBötC region neurons. Reverse transcription-PCR demonstrated the presence of mRNA for Nav1.1, Nav1.2, and Nav1.6 alpha-subunits in individual neurons. A TTX-sensitive I(NaP) was evoked in all tested neurons by ramp depolarization from -80 to 0 mV. Including a constant in the Boltzmann equation for inactivation by estimating the steady-state fraction of Na+ channels available for inactivation allowed prediction of a window current that did not decay to 0 at voltages positive to -20 mV and closely matched the measured I(NaP). Riluzole (3 microM), a putative I(NaP) antagonist, reduced both I(NaP) and I(NaT) and produced a hyperpolarizing shift in the voltage dependence of steady-state inactivation. The latter decreased the predicted window current by an amount equivalent to the decrease in I(NaP). Riluzole also decreased the inactivation time constant at potentials in which the peak window/persistent currents are generated. Together, these findings imply that I(NaP) and I(NaT) arise from the same channels and that a simple modification of the Hodgkin-Huxley model can satisfactorily account for both currents. In the rostral ventral respiratory group (immediately caudal to preBötC), I(NaP) was also detected, but peak conductance, current density, and input resistance were smaller than in preBötC region cells.
Ptak
Krzysztof
K
Department of Physiology and Institute for Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611-3008, USA.
Zummo
Greer G
GG
Alheid
George F
GF
Tkatch
Tatiana
T
Surmeier
D James
DJ
McCrimmon
Donald R
DR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D008526:Medulla Oblongata / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019782:Riluzole / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013266:Stilbamidines; D013779:Tetrodotoxin / Q000494:pharmacology
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D018691:Excitatory Amino Acid Antagonists; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; C568250:Scn1a protein, rat; C568253:Scn2A protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013266:Stilbamidines; D013779:Tetrodotoxin; D019782:Riluzole; D012964:Sodium