ACCOMMODATION OF MOUSE DRG GROWTH CONES TO ELECTRICALLY-INDUCED COLLAPSE - KINETIC-ANALYSIS OF CALCIUM TRANSIENTS AND SET-POINT THEORY

Electrical stimulation causes growth cones of mouse dorsal root gangli on neurons to collapse. During chronic stimulation, however, growth co nes resume motility. In addition, these growth cones are now resistant to the collapsing effects of subsequent stimulation, a process we ter m accommodation. We compared the kinetics of electrically induced Ca2 transients in naive and accommodated growth cones in order to determi ne whether the accommodation process results from a change in the Ca2 transient, or a change in the Ca2+ sensitivity of the growth cones. T hree kinetics were determined: (I ) the initial increase to peak Ca2levels produced by 10 Hz stimulation; (2) recovery from peak Ca2+ leve ls during stimulus trains lasting 15 min; and (3) clearing of Ca2+ fro m growth cones after terminating the stimulus. These kinetics were ana lyzed using single exponential fits to changes in fura-2 fluorescence ratios. The electrically evoked increase in Ca2+ was significantly slo wer in accommodated growth cones (tau = 6.0 s) compared to naive growt h cones (tau = 1.4 s). Despite the slower increase of [Ca2+]i in accom modated growth cones, peak [Ca2+]i was similar to that reached in naiv e growth cones, and the steady-state Ca2+ level was significantly elev ated after chronic stimulation. Thus, accommodated growth cones mainta ined outgrowth at [Ca2+]i that caused collapse initially. Time course experiments show that accommodation is a slow process (t1/2 = about 3 h). Accommodation did not induce measurable changes in the rates of Ca 2+ homeostasis during or after stimulus trains. The kinetics of Ca2+ r ecovery during (tau = 90 s) and after 15 min of stimulation (tau = 8.5 s) was not significantly different in accommodated versus naive growt h cones. Rates of (Ca2+)-Ca-45 efflux were also similar in both types of growth cones. These results suggest two regulatory processes contri buting to growth cone motility during chronic stimulation: (1) recover y of [Ca2+]- to levels permissive to neurite outgrowth, and (2) an inc rease in the range of optimal [Ca2+]i for growth cone motility. These adaptive responses of mammalian growth cones to chronic stimulation co uld be involved in the modulation of CNS development by electrical act ivity of neurons. (C) 1993 John Wiley Sons, Inc.