Inhibition of L-type Ca(2+) channels by curcumin requires a novel protein kinase-theta isoform in rat hippocampal neurons.

In this study, we report that curcumin selectively inhibits L-type Ca(2+) channel currents in cultured rat hippocampal neurons. Whole-cell currents were recorded using 10mM barium as a charge carrier. Curcumin reversibly inhibited high-voltage-gated Ca(2+) channel (HVGCC) currents (I(Ba)) in a concentration-dependent manner but had no apparent effects on the cells treated with nifedipine, a specific L-type Ca(2+) channel blocker. Curcumin did not markedly affect the activation of L-type Ca(2+) channels while significantly shifted the inactivation curve in the hyperpolarizing direction. Pretreatment of cells with the classical and novel PKC antagonists GF109203X and calphostin C completely abolished curcumin-induced I(Ba) inhibition, whereas the classical PKC antagonist Gö6976 or inhibition of PKA activity elicited no such effects. Moreover, the curcumin-induced I(Ba) response was abolished by intracellular application of the PKC-θ inhibitory peptide PKC-θ-IP or by siRNA knockdown of PKC-θ in cultured rat hippocampal neurons. In these neurons, novel isoforms of PKC including delta (PKC-δ), epsilon (PKC-ɛ) and theta (PKC-θ), but not eta (PKC-η), were endogenously expressed. Taken together, these results suggest that curcumin selectively inhibits I(Ba)via a novel PKC-θ-dependent pathway, which could contribute to its neuroprotective effects in rat hippocampal neurons. PMID: 23261315 [PubMed - as supplied by publisher]
Source: Cell Calcium - Category: Cytology Authors: Tags: Cell Calcium Source Type: research