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Differential effects of protein kinase C activation on 5‐HT1A receptor coupling to Ca2+ and K+ currents in rat serotonergic neurones.
Author(s) -
Chen Y,
Penington N J
Publication year - 1996
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.1996.sp021670
Subject(s) - protein kinase c , staurosporine , endocrinology , chemistry , phorbol , medicine , receptor , serotonergic , 5 ht1a receptor , 5 ht receptor , biophysics , biology , serotonin , signal transduction , biochemistry
1. Activation of the enzyme protein kinase C (PKC) partially uncouples receptors from the inhibition of Ca2+ current. We have studied the effect of PKC activation on 5‐HT1A receptor coupling of Ca2+ currents and 5‐HT‐induced K+ current (IK,5‐HT) in acutely isolated adult rat dorsal raphe neurones. 2. The phorbol ester 4 beta‐phorbol 12‐myristate, 13‐acetate (PMA; 1 microM) did not significantly alter the peak Ca2+ current. A maximal dose of 5‐HT inhibited Ca2+ current on average by 52%; after application of PMA, the inhibition was only 30% and the effect was irreversible for the duration of the experiment. 3. The inactive phorbol ester 4 alpha‐phorbol (1 microM) did not reduce the effectiveness of 5‐HT. When the kinase inhibitor staurosporine (ST; 200 nM) was added, PMA reduced the effect of 5‐HT by only 13.9%. ST partially prevented or reversed the effect of PMA, depending on the order of addition. 4. The voltage‐dependent rate or re‐inhibition by 5‐HT was reduced by PMA, suggesting that fewer activated G‐protein subunits are available to interact with Ca2+ channel after the action of PMA. 5. In contrast, PMA (1 microM) did not have a significant effect on IK,5‐HT. 6. PKC activation has an inhibitory effect on one branch of the 5‐HT1A receptor transduction fork, namely inhibition of Ca2+ influx, but not on the activation of IK,5‐HT.