CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 5, Issue 6, 2006

Voltage-gated calcium (Ca2+) channels are heteromeric complexes found in the plasma membrane of virtually all cell types and show a high level of electrophysiological and pharmacological diversity. On the basis of the membrane potential at which they activate, these channels are subdivided into high voltage-activated (HVA) and low voltage-activated (LVA) or transient (Ttype) Ca2+ channels. These channels in nerv Read More

The presence of T-channels in thalamic cells allows for the generation of rhythmic bursts of spikes and the existence of two firing modes in thalamic cells: tonic and bursting. This intrinsic electrophysiological property has fundamental consequences for the functional properties of the thalamus across waking and sleep stages and is centrally implicated in a growing number of pathological states. Rhythmic bursting brings about hi Read More

Voltage-gated calcium channels are found in the plasma membrane of many excitable and non-excitable cells. When open, they permit influx of calcium, which acts as a second messenger to initiate diverse physiological cellular processes. Ten unique α 1 subunits, grouped in three families (CaV1, CaV2, and CaV3), encode biophysically and pharmacologically distinct low-voltage-activated T-type and high-voltage-activated L-t Read More

This review summarizes recent progress on the molecular biology of low voltage-gated, T-type, calcium channels. The genes encoding these channels were identified by molecular cloning of cDNAs that were similar in sequence to the α1 subunit of high voltage-activated Ca2+ channels. Three T-channel genes were identified: CACNA1G, encoding Cav3.1; CACNA1H, encoding Cav3.2; and CACNA1I, encoding Cav3.3. Recent Read More

As T-type calcium channels open near resting membrane potential and markedly influence neuronal excitability their activity needs to be tightly regulated. Few neuronal T-current regulations have been described so far, but interestingly some of them involve unusual mechanisms like G protein-independent but receptor-coupled modulation, while the use of recombinant channels has established both a direct action of Gβ Read More

Thalamocortical neurons in mammals fire action potentials in two different modes, burst or tonic, depending on the cellular state. The burst firing is driven by the low threshold Ca2+ spike that is generated by Ca2+ influx through T-type Ca2+ channels, and has long been implicated in the pathogenesis of absence epilepsy and the regulation of sleep rhythms. The recent availability of the knock-out mice for theα1G locus, e Read More

It is well established that the voltage-gated calcium (Ca2+) channels can modulate neuronal activity in the peripheral and central nervous system causing a variety of behavioral and neuro-endocrine changes in humans and animals. While much attention was focused on the modulation of high voltage-activated (HVA)-type Ca2+ channels, the role of low voltage-activated (LVA) or transient (T) type Ca2+ channels in sensory proc Read More

The electroresponsiveness fingerprint of a neuron reflects the types and distributions of the ionic channels that are embedded in the neuronal membrane as well as its morphology. Theoretical analysis shows that subtle changes in the density of channels can contribute substantially to the electroresponsive fingerprints of neurons. We have confirmed these predictions, using the dynamic clamp approach to emulate changes Read More