The influence of hypocarbia on the resolution of transient increases in brain extracellular potassium

Abstract

The effect of acute hypocarbia on baseline extracellular K+ concentration ([K+](e)) and its effect on the ability of the cerebral microenvironment to recover from transient increases in [K+](e) has been assessed in rats. Spreading depression of cortical activity was used to present a reproducible K+ load to the extracellular space. Baseline [K+](e) and the half-time for resolution of the [K+](e) changes seen with spreading depression waves were measured for the hypocarbic and normocarbic states by means of double-barrelled K+ microelectrodes placed approximately 400 μm below the cortical surface. Three spreading depression waves were initiated in each animal for the two CO2 states. In group 1 (n = 10), the rats were initially normocarbic (Pa(CO2) 41.6 ± 3.0 mmHg; mean ± SD), then hypocarbic (Pa(CO2) 19.0 ± 2.5 mmHg) for the second series of measurements. The baseline [K+](e) was significantly higher in the normocarbic state 3.4 ± 0.4 versus 3.0 ± 0.4 mM l-1, P < 0.01 (paired t test). During normocarbia, the K+ load (Δ[K+](e)) presented to the extracellular space following spreading depression was 49.4 ± 7.5 mM l-1, n = 10 (peak [K+](e) - baseline [K+](e)). The half-time for resolution of the presented [K+](e) load was 24.3 ± 6.1 s. Following hypocarbia of 1.4 ± 0.6 h, there was no change in Δ[K+](e) (49.0 ± 6.0 mM l-1) but resolution t( 1/2 ) had increased to 35.8 ± 11.2 s, P < 0.01 paired t test. For group 2 (n = 10), the opposite experimental sequence was followed with hypocarbia (Pa(CO2) 20.8 ± 1.9 mmHg) established for a mean of 1.4 ± 0.3 h prior to recording session 1. Again, the baseline [K+](e) was higher when the animals were normocarbic 3.3 ± 0.3 versus 3.0 ± 0.5 mM l-1 during hypocarbia, P < 0.05. The half-time for recovery was significantly longer with hypocarbia (33.8 ± 9.3 s) than with subsequent normocarbia (28.8 ± 6.9 s), P < 0.05, despite similar Δ[K+](e) (54.0 ± 6.4 versus 51.6 ± 4.6 mM l-1, respectively). These results demonstrate that, in the non-stressed state, hypcarbia did not induce ischemia at the level of the cerebral microenvironment, as there was no evidence of K+ efflux. However, when a reproducible K+(e) load was presented to the microenvironment, hypocarbia reversibly increased the time required to clear such a K+(e) load by 20-50%. This increase in half-time for resolution of the presented K+(e) load suggests hypocarbia to a Pa(CO2) of 20 mm Hg has a modest and reversible impact on K+(e) clearance compared to experimentally induced stresses, such as ischemia, anoxia, or profound hypoglycemia.