Neurophysiology, VoL 29, No. 6, 1997 REVIEWS Role of Calcineurin in Regulation of High Voltage-Activated Calcium Channel Activity E. A. Lukyanetz I Neirofiziologiya/Neurophysiology, Vol. 29, No. 6, pp. 442-447, November-December, 1997. Received July 24, 1997. In the Review, personal data of the Author and the data of other experimenters on calcium/calmodulin-dependent protein pho~phatase-2B (calcineurin) are summarized and analyzed; the role of this enzyme in regulation of the calcium channel activity in the membrane of excitable cells is discussed. A two-phase mechanism of Ca-dependent suppression of the activity of Ca channels in the molluscan neurons is described in details. Special attention is paid to the analysis of changes in the activity of Ca channels in the transfected hybrid cells overexpressing calcineurin. ENZYMES INVOLVED IN THE PROCESSES OF DEPHOSPHORYLATION l~egulation of various intracellular systems in many cases includes phosphorylation reactions, and the mechanisms connected with the processes of dephos- phorylation of the substrate provide termination of a response; it is obvious that the latter mechanisms are very important for the whole process of regulation. Dephosphorylation is carried out by a particular class of proteins -- enzymes named protein phosphatases, which apparently are not the components of some definite system of secondary messengers. We believe that protein phosphatases together with their natural modulators have to be considered independent en- zymatic systems. Protein phosphatases can be separated into two wide groups differing according to their substrate of dephosphorylation and designated as protein phos- I Bogomolels Institute of Physiology, National Academy of Sciences of Ukraine, Kiev, Ukraine. 352 phatases of type 1 and type 2 (PP1 and PP2, respec- tively) [1-3]. PP2 in turn is classified into three subtypes (PP2A, 2B, and 2C) according to the substrate specificity, size and composition of the molecule, and also cation dependence. It was demonstrated that the activity of protein phosphatases can be blocked by natural thermostable proteins: Inhibitor-1 and Inhi- bitor-2; their activity is noticeably lower with respect to PP2. Calcineurin, or protein phosphatase-2B (PP2B), is Ca-dependent calmodulin-stimulated protein phospha- tase (EC 3.1.3.16) [4]; it is known as the only form of phosphatases that is handled by Ca ions. CALCINEURIN Currently it has been established that PP2B is the main Ca/calmodulin-dependent protein present in the brain [5 ]. Calcineurin consists of two subunits named A and B, and their molar ratio is equal to 1:1. Subunit A is the catalytic component interacting with cap modulin, whereas B subunit is the Ca2%binding com- ponent and contributes the enzyme binding. Two specific peculiarities are characteristic for calcineurin: o 0090-2977/97/29~6-0352518.00 1998 Plenum Publishing Corporation