Activity-dependent intracellular acidification correlates with the duration of seizure activity

Synchronized neuronal activity (seizures) can appear in the presence or abs ence of synaptic transmission. Mechanisms of seizure initiation in each of these conditions have been studied, but relatively few studies have address ed seizure termination. In particular, how are seizures terminated in the a bsence of synaptic activity where there is no loss of excitatory drive or a ugmentation of inhibitory inputs? We have studied dynamic activity-dependen t changes of intracellular pH in the absence of synaptic transmission using the fluorescent pH indicator carboxylseminaphthorhodafluo-1. During epilep tiform activity we observed intracellular acidification, whereas between se izures the intracellular pH recovered. Experimental conditions that shorten ed the epileptiform discharge correlated with more rapid intracellular acid ification. On the other hand, experimental manipulation of intracellular pH altered the duration of the seizure discharge, with acidification resultin g in early termination of the epileptiform activity. These data show a dire ct relationship between the level of intracellular acidification and the du ration of the seizures, suggesting that an intracellular pH-dependent proce ss can terminate nonsynaptic neuronal synchronization.