Three distinct α 1 subunit genes encode T-type Ca 2+ channels (Ca V 3.1, Ca V 3.2, and Ca V 3.3), and these have nonredundant roles in pain transmission, cell proliferation, and cardiovascular function. Lysophosphatidic acid (LPA), a phospholipid involved in the development and growth of neurons, binds to members of a family of G protein-coupled receptors (GPCRs) called LPA1-5, of which LPA1 is the most abundant in the brain. LPA1 activates members of the Gα i , Gα q , and Gα 12/13 family of G proteins. Stimulated Gα 12/13 activates the Rho guanosine triphosphatase family member RhoA, which activates Rho-associated kinase (ROCK). ROCK isoforms phosphorylate (among other substrates) sodium and potassium channels. Previous studies have shown overlapping physiological responses to activation of either ROCK or T-type Ca 2+ channels, so Iftinca et al . investigated a role for ROCK in regulating T-type Ca 2+ channels. Whole-cell patch clamp assays on tsA-201 cells (a subclone of HEK 293 cells) transiently expressing rat Ca V 3.1 showed a dose-dependent decrease in channel current in response to LPA. Experiments with pertussis toxin (to block Gα i ) and protein kinase C inhibitors (to block signals downstream of Gα q ) suggested that the Gα 12/13 pathway mediated the inhibitory effect of LPA on Ca V 3.1 activity. Coexpression of dominant-negative mutants of Gα 12 and Gα 13 , or treatment with specific inhibitors of Rho or ROCK, substantially decreased the inhibitory effects of LPA. Mutation of Ser and Thr residues in putative ROCK-phosphorylation consensus sites (found between domains II and III) of Ca V 3.1 resulted in mutant channels that did not respond to LPA. These consensus sites are conserved in all T-type Ca 2+ channels, and the authors found that whereas LPA treatment also inhibited the activity of Ca V 3.3, it increased the activity of Ca V 3.2. The authors performed experiments in neurons isolated from the lateral habenula (LHb) nucleus (predominantly expressing Ca V 3.1) and the dorsal root ganglia (DRG, in which Ca V 3.2 is the major channel) of rats and found that the effects of LPA (decreasing currents in LHb neurons and increasing currents in the DRG) were all blocked by inhibition of ROCK. Together, these data describe a new mechanism of regulation of the activity of T-type Ca 2+ channels and, given that T-type Ca 2+ channels and ROCK are coexpressed in other cell types, suggest that this regulation might be important for various physiological processes. M. Iftinca, J. Hamid, L. Chen, D. Varela, R. Tadayonnejad, C. Altier, R. W. Turner, G. W. Zamponi, Regulation of T-type calcium channels by Rho-associated kinase. Nat. Neurosci. 10 , 854-860 (2007). [PubMed]