Dendritic distributions of L-ypeCa2+and SKLchannels in spinal motoneurons: a simulation study.J Neurophysiol124: 1285–1307, 2020. First published September16, 2020; doi:10.1152/jn.00169.2020.—Persistent inward currentsare important to motoneuron excitability and firing behaviors andalso have been implicated in excitotoxicity. In particular, L-typeCa2+channels, usually located on motoneuron dendrites, play a pri-mary role in amplification of synaptic inputs. However, recent ex-perimental findings on L-type Ca2+channel behaviors challengesome fundamental assumptions that have been used in interpretingexperimental and computational modeling data. Thus, the objectivesof this study were to incorporate recent experimental data into anupdated, high-fidelity computational model in order to explainapparent inconsistencies and to better elucidate the spatial distribu-tions, expression patterns, and functional roles of L-type Ca2+andSKLchannels. Specifically, the updated model incorporated asym-metric channel activation/deactivation kinetics, depolarization-de-pendent facilitation, randomness in channel gating, and coactivationof SKLchannels. Our simulation results suggest that L-type Ca2+and SKLchannels colocalize primarily on distal dendrites of moto-neurons in a punctate expression. Also, punctate expression, asopposed to a homogeneous expression, provides high synaptic cur-rent amplification, limits bistability and firing rates, and robustlyregulates the Ca2+persistent inward current, thereby reducing riskof excitotoxicity. The hysteresis and bistability observed experimen-tally in current-voltage and frequency-current relationships resultfrom the L-type Ca2+channels’ distal location and intrinsic warm-up. Accordingly, our results indicate that punctate expression of L-type Ca2+and SKLchannels is a potent mechanism for regulatingexcitability, which would provide a strong neuroprotective effect.Our results could provide broader insights into the functional signif-icance of warm-up and punctate expression of ion channels to regu-lation of cell excitability.NEW & NOTEWORTHYRecent experimental findings on L-typeCa2+channels challenge fundamental assumptions used in interpret-ing experimental and computational modeling data. Here, we incor-porated recent experimental data into an updated, high-fidelitycomputational model to explain apparent inconsistencies and betterelucidate the distributions, expression patterns, and functional rolesof L-type Ca2+and SKLchannels. Our results indicate that punctateexpression of L-type Ca2+and SKLchannels is a potent mechanismfor regulating motoneuron excitability, providing a strong neuropro-tective effect.