Chemosensitivity of non-respiratory rat CNS neurons in tissue culture

Abstract

Neurons from many brainstem nuclei involved in respiratory control increase their firing rate in response to acidosis in vitro, suggesting that they are central chemoreceptors. This property has been considered to be either unique to neurons involved in respiratory control, or at least very unusual for non-respiratory neurons. However, recordings of intrinsic pH responses of neurons have not been made from enough non-respiratory regions of the CNS to be certain this assumption is true. Here, we have quantified changes in firing rate of neurons cultured from the hippocampus ( n=43), neocortex ( n=33), and cerebellum ( n=29) in response to changes in CO 2 between 3% and 9% (pH≈7.6–7.2) after blockade of glutamatergic and GABAergic transmission. The responses of neurons from these three regions were similar, with a subset of neurons (12% of the total 105) inhibited by acidosis, decreasing their firing rate to a mean of 70% of control in response to a decrease in pH of 0.2. Some neurons (5% of total) were stimulated by acidosis, with an increase in firing rate to a mean of 175% of control in response to a decrease in pH of 0.2. We previously quantified chemosensitivity of neurons from the medullary raphe using the same methods [W. Wang, J.H. Pizzonia, G.B. Richerson, Chemosensitivity of rat medullary raphe neurones in primary tissue culture, J. Physiol., 511 (1998) 433–450]. Compared to these non-respiratory neurons, more raphe neurons were stimulated by acidosis (22%), and the average response was greater (to 300% of control) in response to the same stimulus. Thus, over a physiologically relevant pH range, stimulation by acidosis occurs in a significant percentage of neurons not involved in respiratory chemoreception. However, the degree of chemosensitivity of these neurons was less than medullary raphe neurons under the same conditions. Chemosensitivity is not an all-or-none neuronal property, and the degree of chemosensitivity may be relevant to the role neurons play in sensing pH in vivo.