Heparin/heparan sulfates bind to and modulate neuronal L-type (Cav1.2) voltage-dependent Ca(2+) channels.

Heparin/heparan sulfates bind to and modulate neuronal L-type (Cav1.2) voltage-dependent Ca(2+) channels.
Exp Neurol. 2015 Aug 10;
Authors: Garau G, Magotti P, Heine M, Korotchenko S, Lievens PM, Berezin V, Dityatev A
Abstract
Our previous studies revealed that L-type voltage-dependent Ca(2+) channels (Cav1.2L-VDCCs) are modulated by the neural extracellular matrix backbone, polyanionic glycan hyaluronic acid. Here we used isothermal titration calorimetry and screened a set of peptides derived from the extracellular domains of Cav1.2α1 to identify putative binding sites between the channel and hyaluronic acid or another class of polyanionic glycans, heparin/heparan sulfates. None of the tested peptides showed detectable interaction with hyaluronic acid, but two peptides derived from the first pore-forming domain of Cav1.2α1 subunit bound to heparin. At 25°C the binding of the peptide P7 (MGKMHKTCYN) was at ~50μM, and that of the peptide P8 (GHGRQCQNGTVCKPGWDGPKHG) was at ~21μM. The Cav1.2α1 first pore forming segment that contained both peptides maintained a high affinity for heparin (~23μM), integrating their enthalpic and entropic binding contributions. Interaction between heparin and recombinant as well as native full-length neuronal Cav1.2α1 channels was confirmed using the heparin-agarose pull down assay. Whole cell patch clamp recordings in HEK293 cells transfected with neuronal Cav1.2 channels revealed that enzymatic d...

Source: Experimental Neurology - August 10, 2015 Category: Neurology Authors: Garau G, Magotti P, Heine M, Korotchenko S, Lievens PM, Berezin V, Dityatev A Tags: Exp Neurol Source Type: research