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Kinetic, pharmacological and activity‐dependent separation of two Ca 2+ signalling pathways mediated by type 1 metabotropic glutamate receptors in rat Purkinje neurones
Author(s) -
Canepari Marco,
Ogden David
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.103770
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 1 , chemistry , metabotropic receptor , biophysics , apamin , glutamate receptor , ionotropic effect , stimulation , iberiotoxin , neuroscience , receptor , biochemistry , potassium channel , biology
Type 1 metabotropic glutamate receptors (mGluR1) in Purkinje neurones (PNs) are important for motor learning and coordination. Here, two divergent mGluR1 Ca 2+ ‐signalling pathways and the associated membrane conductances were distinguished kinetically and pharmacologically after activation by 1‐ms photorelease of l ‐glutamate or by bursts of parallel fibre (PF) stimulation. A new, mGluR1‐mediated transient K + conductance was seen prior to the slow EPSC (sEPSC). It was seen only in PNs previously allowed to fire spontaneously or held at depolarized potentials for several seconds and was slowly inhibited by agatoxin IVA, which blocks P/Q‐type Ca 2+ channels. It peaked in 148 ms, had well‐defined kinetics and, unlike the sEPSC, was abolished by the phospholipase C (PLC) inhibitor U73122. It was blocked by the BK Ca 2+ ‐activated K + channel blocker iberiotoxin and unaffected by apamin, indicating selective activation of BK channels by PLC‐dependent store‐released Ca 2+ . The K + conductance and underlying transient Ca 2+ release showed a highly reproducible delay of 99.5 ms following PF burst stimulation, with a precision of 1–2 ms in repeated responses of the same PN, and a subsequent fast rise and fall of Ca 2+ concentration. Analysis of Ca 2+ signals showed that activation of the K + conductance by Ca 2+ release occured in small dendrites and subresolution structures, most probably spines. The results show that PF burst stimulation activates two pathways of mGluR1 signalling in PNs. First, transient, PLC‐dependent Ca 2+ release from stores with precisely reproducible timing and second, slower Ca 2+ influx in the cation‐permeable sEPSC channel. The priming by prior Ca 2+ influx in P/Q‐type Ca 2+ channels may determine the path of mGluR1 signalling. The precise timing of PLC‐mediated store release may be important for interactions of PF mGluR1 signalling with other inputs to the PN.