The Yin and Yang of the H-Channel and Its Role in Epilepsy.

Voltage-gated ion channels clearly are involved in the pathogenesis of epilepsy, with evidence implicating derangement of Na(+), K(+), and Ca(2+) voltage-gated channels, in both inherited and acquired forms of epilepsy ((1)). A newcomer to this list of ion channels involved in epilepsy is the hyperpolarization-activated cation channel or h-channel (otherwise known as I(h) or the pacemaker channel). This voltage-gated channel now is known to play a significant role in regulating neuronal excitability and recently has been shown to be modulated by seizures. Unlike other channels implicated in epilepsy whose function in normal neurons can clearly be labeled "excitatory" (Na(+) and Ca(2+)) or "inhibitory" (K(+)), the unique physiologic behavior of the h-channel allows it to both augment and decrease the excitability of neurons. Thus the role of I(h) in epilepsy, at present, is controversial and is a growing area of intense investigation ((2)(3)).