Acidosis, associated with metabolic disorders, leads to the pathological changes of cognition and behavior in the clinical practices of neurology and psychology. The cellular mechanisms underlying these cerebral dysfunctions remain unclear. By using electrophysiological approach and changing extracellular pH, we have investigated the effects of acidic environment on cortical GABAergic neurons in terms of their abilities of firing spikes and responses to synaptic inputs. Artificial cerebral spinal fluid in low pH impairs the responses to excitatory synaptic inputs and the abilities of encoding sequential spikes at these GABAergic neurons. The impairments of neuronal spiking are associated with the increases of refractory periods and threshold potentials. Our studies reveal that acidosis may impair cortical GABAergic neurons and in turn deteriorate brain functions, in which their final targets are voltage-gated sodium channels and glutamate receptor-channels. (C) 2011 Elsevier Inc. All rights reserved.