Differential contributions of somatic and dendritic calcium-dependent potassium currents to the control of motoneuron excitability following spinal cord injury |
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Authors: | Sharmila Venugopal Thomas M Hamm Ranu Jung |
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Institution: | (1) Department of Integrative Biology & Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA;(2) Division of Neurobiology, Barrow Neurological Institute, St. Joseph’s Hospital, Phoenix, AZ 85013, USA;(3) Department of Biomedical Engineering, Florida International University, EC 2602, 10555 W Flagler Street, Miami, FL 33174, USA; |
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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. |
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Keywords: | Motoneuron model Persistent inward currents Spinal cord injury Steady-state analysis Calcium currents Calcium dependent potassium currents Dendritic currents Hyperexcitability Spasticity |
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