Activity-dependent extracellular K+ accumulation in rat optic nerve:: the role of glial and axonal Na+ pumps

1. We measured activity-dependent changes in [K+](o) with K+-selective microelectrodes in adult rat optic nerve, a CNS white matter tract, to investigate the factors responsible for post-stimulus recovery of [K+](o). 2. Post-stimulus recovery of [K+](o) followed a double-exponential time course with an initial, fast time constant, tau(fast), of 0.9 +/- 0.2 s (mean +/- S.D) and a later, slow time constant, tau(slow), of 4.2 +/- 1 s following a 1 s, 100 Hz stimulus. tau(fast), but not tau(slow), decreased with increasing activity-dependent rises in [K+](o). tau(slow), but not tau(fast), increased with increasing stimulus duration. 3. Post-stimulus recovery of [K+](o) was temperature sensitive. The apparent temperature coefficients (Q(10), 27-37 degrees C) for the fast and slow components following a 1 s, 100 Hz stimulus were 1.7 and 2.6, respectively. 4. Post-stimulus recovery of [K+](o) was sensitive to Na+ pump inhibition with 50 mu M strophanthidin. Following a 1 s, 100 Hz stimulus, 50 mu M strophanthidin increased tau(fast) and tau(slow) by 81 and 464%, respectively. Strophanthidin reduced the temperature sensitivity of post-stimulus recovery of [K+](o). 5. Post-stimulus recovery of [K+](o) was minimally affected by the K+ channel blocker Ba2+ (0.2 mM). Following a 10 a, 100 Hz stimulus, 0.2 mM Ba2+ increased tau(fast) and tau(slow) by 24 and 18%, respectively. 6. Stimulated increases in [K+](o) were followed by undershoots of [K+](o). Post-stimulus undershoot amplitude increased with stimulus duration but was independent of the peak preceding [K+](o) increase. 7. These observations imply that two distinct processes contribute to post-stimulus recovery of [K+](o) in central white matter. The results are compatible with a model of K+ removal that attributes the fast, initial phase of K+ removal to K+ uptake by glial Na+ pumps and the slower, sustained decline to K+ uptake via axonal Na+ pumps.