Lowvoltageactivated

Low-voltage-activated refers to ion channels that open in response to relatively small or hyperpolarized depolarizations, in contrast to high-voltage-activated channels that require stronger depolarization. In neurons the term most often describes T-type calcium channels, which begin to activate around -60 to -40 mV, exhibit rapid inactivation, and contribute to transient, low-threshold currents.

The main molecular mediators of LVA calcium currents are the T-type channels Cav3.1, Cav3.2, and Cav3.3, encoded by CACNA1G, CACNA1H, and CACNA1I, respectively. These channels activate quickly and inactivate within tens of milliseconds, generating window or rebound currents when the membrane is hyperpolarized. Their activity can produce low-threshold spikes and facilitate rebound depolarizations that help to trigger action potential bursts.

Physiologically, LVA currents are prominent in many central neurons, especially in thalamic relay neurons and certain cortical and brainstem neurons. They contribute to rhythmic oscillations, sleep-related activity, and pacemaker-like firing. By enabling rebound excitation after inhibitory inputs, LVA channels influence neuronal excitability and the timing of action potentials, often shaping the pattern rather than the absolute rate of firing.

Pharmacology and clinical relevance include sensitivity to nickel and selective T-type channel blockers such as ethosuximide, which is used to treat absence seizures by reducing low-threshold calcium currents in thalamic neurons. Alterations in LVA channel expression or function have been linked to various neurological conditions, including epilepsy and neuropathic pain, underscoring the role of low-voltage-activated currents in excitability and network dynamics.

In summary, low-voltage-activated channels, chiefly T-type calcium channels, activate at relatively negative potentials, support rapid, transient calcium entry, and play key roles in shaping neuronal excitability and rhythmic activity.