Properties of gap junction blockers and their behavioural, cognitive and electrophysiological effects: animal and human studies

Abstract

Gap junctions play an important role in brain physiology. They synchronize neuronal activity and connect glial cells participating in the regulation of brain metabolism and homeostasis. Gap junction blockers (GJBs) include various chemicals that impair gap junction communication, disrupt oscillatory neuronal activity over a wide range of frequencies, and decrease epileptic discharges. The behavioural and clinical effects of GJBs suggest that gap junctions can be involved in the regulation of locomotor activity, arousal, memory, and breathing. Severe neuropsychiatric side effects suggest the involvement of gap junctions in mechanisms of consciousness. Unfortunately, the available GJBs are not selective and can bind to targets other than gap junctions. Other problems in behavioural studies include the possible adverse effects of GJBs, for example, retinal toxicity and hearing disturbances, changes in blood-brain transport, and the metabolism of other drugs. Therefore, it is necessary to design experiments properly to avoid false, misleading or uninterpretable results. We review the pharmacological properties and electrophysiological, behavioural and cognitive effects of the available gap junction blockers, such as carbenoxolone, glycyrrhetinic acid, quinine, quinidine, mefloquine, heptanol, octanol, anandamide, fenamates, 2-APB, several anaesthetics, retinoic acid, oleamide, spermine, aminosulfonates, and sodium propionate. It is concluded that despite a number of different problems, the currently used gap junction blockers could be useful tools in pharmacology and neuroscience.