Investigation of the primary stimulus and mechanism of the ammonium chloride-induced increase in the content of potassium in choroid plexus epithelial cells

After young adult male rate were injected intraperitoneally with NH4C1, the content of K (hereafter, CP [K]) within the epithelial cells of the choroid plexus increased greatly while that of Na (CP [K]) decreased. This dissertation has focused on elucidating the primary stimulus and mechanism of the NH4C1-induced increase in CP [K], with some investigative focus on the induced decrease in CP [Na]. The primary stimuli under consideration are the NH4C1-induced increases in plasma [NH4], [K]. and [H], and decreases in [HCO3] and [Na]. An acidosis-induced augmentation in the concentration of catecholamines available to CP beta-adrenoceptors has also been considered. Since sympathectomy, adrenalectomy or pretreatment with beta-adrenoceptor blockers did not reduce the effects of NH4C1, it was possible to rule out an involvement of catecholamines as the stimulus. A comparison of the time-courses of plasma [ammonia] with CP [K] and [Na} indicated that the primary stimulus was not plasma [NH4]. A comparison of the effects of nine individual salt treatments on plasma [K] with CP [K] and [Na}, revealed that plasma [K] was not the primary stimulus. Significant statistical correlations were drawn between plasma [H] and the induce increase in CP [K] and decrease in CP [Na]. Since an elevation of plasma [H] was most consistently associated with and increase in CP [K], the mechanism through which [H] operates was investigated. The increase in CP [K] and decrease in CP [Na] must result from wither an increase in Na-k exchange (Na-K Atpase), or from a decrease in K efflux and Na influx; or perhaps a combination of both. With a physiological analog of K (i.e., Rb), it was demonstrated that acidosis does not increase the slope of the initial ‘linear uptake of 86Rb in vitro; thus no effect of acidosis to increase Na-Rb exchange (i.e., Na-K exchange) was found. Since acidosis augments the steady-state volume of distribution of 86Rb in vitro, without an increase in Na-Rb exchange, it would appear that acidosis augments CP Rb by effecting a reduction in Rb efflux and, by analogy, would also reduce the efflux of CP K. In conclusion, NH4C1 induces an increase in CP [K] by increasing plasma [H] which in turn acts to reduce the efflux of K across the apical and/or basolateral membranes of the CP. An in vivo indication that acidosis reduces the efflux of K across the apical membrane was suggested by a decrease in CSF [K].