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The cytosolic II–III loop of Ca v 2.3 provides an essential determinant for the phorbol ester‐mediated stimulation of E–type Ca 2+ channel activity
Author(s) -
Klöckner Udo,
Pereverzev Alexey,
Leroy Jérôme,
Krieger Andreas,
Vajna Rolf,
Pfitzer Gabriele,
Hescheler Jürgen,
Malécot Claire O.,
Schneider Toni
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.0953-816x.2004.03375.x
Subject(s) - bisindolylmaleimide , protein kinase c , stimulation , biophysics , chemistry , cytosol , phorbol , context (archaeology) , phosphorylation , microbiology and biotechnology , biology , biochemistry , endocrinology , enzyme , paleontology
There is growing evidence that E‐type voltage dependent Ca 2+ channels (Ca v 2.3) are involved in triggering and controlling pivotal cellular processes like neurosecretion and long‐term potentiation. The mechanism underlying a novel Ca 2+ dependent stimulation of E‐type Ca 2+ channels was investigated in the context of the recent finding that influx of Ca 2+ through other voltage dependent Ca 2+ channels is necessary and sufficient to directly activate protein kinase C (PKC). With Ba 2+ as charge carrier through Ca v 2.3 channel α 1 subunits expressed in HEK‐293 cells, activation of PKC by low concentrations of phorbol ester augmented peak I Ba by approximately 60%. In addition, the non‐inactivating fraction of I Ba was increased by more than three‐fold and recovery from short‐term inactivation was accelerated. The effect of phorbol ester on I Ba was inhibited by application of the specific PKC inhibitor bisindolylmaleimide I. With Ca 2+ as charge carrier, application of phorbol ester did not change the activity of Ca v 2.3 currents but they were modified by the PKC inhibitor bisindolylmaleimide I. These results suggest that with Ca 2+ as charge carrier the incoming Ca 2+ can activate PKC, thereby augmenting Ca 2+ influx into the cytosol. No modulation of Ca v 2.3 channels by PKC was observed when an arginine rich region in the II–III loop of Ca v 2.3 was eliminated. Receptor independent stimulation of PKC and its interaction with Ca v 2.3 channels therefore represents an important positive feedback mechanism to decode electrical signals into a variety of cellular functions.