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The Journal of Neuroscience, May 25, 2005, 25(21):5159-5170; doi:10.1523/JNEUROSCI.4238-04.2005

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Behavioral/Systems/Cognitive
Sodium Currents in Medullary Neurons Isolated from the Pre-Bötzinger Complex Region

Krzysztof Ptak, Greer G. Zummo, George F. Alheid, Tatiana Tkatch, D. James Surmeier, and Donald R. McCrimmon

Department of Physiology and Institute for Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611-3008

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 -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 µM), 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.

Key words: sodium channels; persistent current; respiration; pre-Bötzinger; pacemaker; riluzole; central pattern generator

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Received Feb 11, 2004; revised April 14, 2005; accepted April 14, 2005.

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