Several types of voltage- or ligand-activated calcium channels contribute to the 
excitability of neuronal cells. Low-voltage-activated (LVA), T-type calcium 
channels are characterised by relatively negative threshold of activation and 
therefore they can generate low-threshold spikes, which are essential for burst 
firing. At least three different proteins form T-type calcium current in 
neurons: Ca(v)3.1, Ca(v)3.2 and Ca(v)3.3. Expression of these proteins in 
various brain regions is complementary. Individual channel types could be 
distinguished by different sensitivity towards inorganic cations. This 
inhibition can contribute to the toxicity of some heavy metals. Selective 
inhibition of T-type calcium channels by organic blockers may have clinical 
importance in some forms of epilepsy. Mibefradil inhibits the expressed 
Ca(v2)3.1, Ca(v)3.2 and Ca(v)3.3 channels in nanomolar concentrations with 
Ca(v)3.3 channel having lowest affinity. The sensitivity of the expressed 
Ca(v)3.1 channel to the antiepileptic drugs, valproate and ethosuximide, is low. 
Ca(v)3.1 channel is moderately sensitive to phenytoin. The Ca(v)3.2 channel is 
sensitive to ethosuximide, amlodipine and amiloride. All three LVA calcium 
channels are moderately sensitive to active metabolites of methosuximide, i.e. 
alpha-methyl-alpha-phenylsuccinimide. Several neuroleptics inhibit all three LVA 
channels in clinically relevant concentrations. All three channels are also 
inhibited by the endogenous cannabinoid anandamide. A high affinity peptide 
blocker for these Ca channels is the scorpion toxin kurtoxin which inhibits the 
Ca(v)3.1 and Ca(v)3.2, but not the Ca(v)3.3 channel in nanomolar concentrations. 
Nitrous oxide selectively inhibits the Ca(v)3.2, but not the Ca(v)3.1 channel. 
The Ca(v)3.2, but not the Ca(v)3.1 channel is potentiated by stimulation of 
Ca(2+)/CaM-dependent protein kinase.