Cytosolic segments of membrane-bound voltage-gated Ca²⁺ channels bind specific signalling complexes, which transfer information to physiological processes via soluble protein interaction partners. The molecular chaperone Hsp70 was identified by recombinant technologies and mass spectrometry as a binding partner for the cytosolic II-III loop of Ca_v2.3 (Krieger et al., 2006). To test its functional significance in vivo, two approaches were chosen. First, we applied Hsp70 linked to a cell membrane penetrating peptide, to stably Ca_v2.3 transfected HEK-293 cells, and the cells were analysed by whole cell Ca²⁺ current recordings. Secondly, in hippocampal microsomes from control mice, hsp70 binding was increased, when kainate (20 mg/kg, i.p.) was injected at concentrations which induce seizures and neurodegeneration. However, in Ca_v2.3-deficient mice only mild seizures were observed after kainate injection with no hippocampal neurodegeneration and no increase in hsp70 binding to the membrane fraction of isolated hippocampal microsomes, indicating that hsp70 maybe an important intermediate signalling partner to prevent hippocampal neurodegeneration.

Supported by Köln-Fortune and Center for Molecular Medicine Cologne (CMMC).

Krieger Andreas, Kayalvizhi Radhakrishnan, Alexey Pereverzev, Siarhei A. Siapich, Mohammed Banat, Marcel A. Kamp, Jérôme Leroy, Udo Klöckner, Jürgen Hescheler, Marco Weiergräber, Toni Schneider (2006) The molecular chaperone hsp70 interacts with the cytosolic II-III loop of the Cav2.3 E-type voltage-gated Ca²⁺ channel. Cell Physiol Biochem. 17, 97–110.