title: Differential contributions of somatic and dendritic calcium-dependent potassium currents to the control of motoneuron excitability following spinal cord injury.
abstract: The hyperexcitability of alpha-motoneurons and accompanying spasticity following spinal cord injury (SCI) have been attributed to enhanced persistent inward currents (PICs), including L-type calcium and persistent sodium currents. Factors controlling PICs may offer new therapies for managing spasticity. Such factors include calcium-activated potassium (KCa) currents, comprising in motoneurons an after-hyperpolarization-producing current (I KCaN) activated by N/P-type calcium currents, and a second current (I KCaL) activated by L-type calcium currents (Li and Bennett in J neurophysiol 97:767-783, 2007). We hypothesize that these two currents offer differential control of PICs and motoneuron excitability based on their probable somatic and dendritic locations, respectively. We reproduced SCI-induced PIC enhancement in a two-compartment motoneuron model that resulted in persistent dendritic plateau potentials. Removing dendritic I KCaL eliminated primary frequency range discharge and produced an abrupt transition into tertiary range firing without significant changes in the overall frequency gain. However, I KCaN removal mainly increased the gain. Steady-state analyses of dendritic membrane potential showed that I KCaL limits plateau potential magnitude and strongly modulates the somatic injected current thresholds for plateau onset and offset. In contrast, I KCaN had no effect on the plateau magnitude and thresholds. These results suggest that impaired function of I KCaL may be an important intrinsic mechanism underlying PIC-induced motoneuron hyperexcitability following SCI.
authors.affiliation: Department of Integrative Biology & Physiology, University of California Los Angeles, Los Angeles, CA 90095 USA.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Venugopal
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Hamm
authors.forename: Ranu
authors.initials: R
authors.lastname: Jung
keywords: Calcium currents; Calcium dependent potassium currents; Dendritic currents; Hyperexcitability; Motoneuron model; Persistent inward currents; Spasticity; Spinal cord injury; Steady-state analysis