In larval lamprey, hemitransections were performed on the right side of the rostral spinal cord to axotomize ipsilateral reticulospinal (RS) neurons. First, at short recovery times (2-3 weeks), uninjured RS neurons contralateral to hemitransections fired a smooth train of action potentials in response to sustained depolarization, whereas axotomized neurons fired a single short burst or short repetitive bursts. For uninjured RS neurons, the afterpotentials of action potentials had three components: fast afterhyperpolarization (fAHP), afterdepolarizing potential (ADP), and slow AHP (sAHP) that was attributable to calcium influx via high-voltage-activated (HVA) (N-and P/Q-type) calcium channels and calcium-activated potassium channels (SKKCa). For axotomized RS neurons, the fAHP was significantly larger than for uninjured neurons, and the ADP and sAHP were absent or significantly reduced. Second, at relatively long recovery times (12-16 weeks), axotomized RS neurons displayed firing patterns and afterpotentials that were similar to those of uninjured neurons. Third, mRNA levels of lamprey HVA calcium and SKKCa channels in axotomized RS neurons were significantly reduced at short recovery times and restored at long recovery times. Fourth, blocking calcium channels in uninjured RS neurons resulted in altered firing patterns that resembled those produced by axotomy. We demonstrated previously that lamprey RS neurons in culture extend neurites, and calcium influx results in inhibition of neurite outgrowth or retraction. Together, these results suggest that the downregulation of Ca 2ϩ channels in axotomized RS neurons, and the associated reduction in calcium influx, maintain intracellular calcium levels in a range that is permissive for axonal regeneration.

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