Intrinsic neuronal excitability: implications for health and disease

The output of a single neuron depends on both synaptic connectivity and intrinsic membrane properties. Changes in both synaptic and intrinsic membrane properties have been observed during homeostatic processes (e.g., vestibular compensation) as well as in several central nervous system (CNS) disorders. Although changes in synaptic properties have been extensively studied, particularly with regard to learning and memory, the contribution of intrinsic membrane properties to either physiological or pathological processes is much less clear. Recent research, however, has shown that alterations in the number, location or properties of voltage- and ligand-gated ion channels can underlie both normal and abnormal physiology, and that these changes arise via a diverse suite of molecular substrates. The literature reviewed here shows that changes in intrinsic neuronal excitability (presumably in concert with synaptic plasticity) can fundamentally modify the output of neurons, and that these modifications can subserve both homeostatic mechanisms and the pathogenesis of CNS disorders including epilepsy, migraine, and chronic pain.