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Serotonergic modulation of persistent sodium currents and membrane excitability via cyclic AMP‐protein kinase A cascade in mesencephalic V neurons
Author(s) -
Tanaka Susumu,
Chandler Scott H.
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20822
Subject(s) - forskolin , protein kinase a , chemistry , biophysics , endocrinology , membrane potential , intracellular , medicine , camp dependent pathway , stimulation , microbiology and biotechnology , biology , kinase , biochemistry
In rat mesencephalic trigeminal (Mes V) neurons, persistent sodium currents in conjunction with low‐threshold potassium currents are critical for generation of subthreshold membrane oscillations and onset of burst behavior. Here we demonstrate that the cAMP/protein kinase A (PKA) signaling pathway modulates persistent sodium currents. In particular, we show that elevation of cAMP suppresses a low‐threshold I NaP via a PKA intracellular pathway. Bath application of forskolin (20 μM), a stimulant for the production of cAMP, reduced the peak I NaP . 1,9‐Dideoxy‐forskolin (20 μM), an inactive form of forskolin, produced minimal effects on I NaP , and the membrane‐permeable cAMP analogue 8‐bromo‐cAMP (500 μM) mimicked the effect of forskolin. Additionally, preapplication of H89 (2 μM), a specific PKA inhibitor, suppressed the effect of forskolin, suggesting the involvement of the cAMP/PKA intracellular signaling pathway in this modulation. 5‐HT receptor stimulation (20 μM) also mimicked the modulation of I NaP by forskolin via the cAMP/PKA‐dependent signaling pathway. Current clamp analysis demonstrated that voltage‐dependent membrane resonance in response to a ZAP input current at depolarized holding potentials (approximately –50 mV) was specifically suppressed by forskolin or 5‐HT. Moreover, drug application enhanced frequency adaptation in response to a 1‐sec current pulse. These results indicate that modulation of persistent sodium currents by a cAMP/PKA pathway can significantly alter the membrane excitability and discharge characteristics of Mes V neurons. © 2006 Wiley‐Liss, Inc.