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PKA‐mediated inhibition of a novel K + channel underlies the slow after‐hyperpolarization in enteric AH neurons
Author(s) -
Vogalis Fivos,
Harvey John R.,
Furness John B.
Publication year - 2003
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 - 10.1111/j..2003.t01-1-00801.x
Subject(s) - forskolin , hyperpolarization (physics) , gating , chemistry , biophysics , patch clamp , inhibitory postsynaptic potential , protein kinase a , membrane potential , microbiology and biotechnology , potassium channel , electrophysiology , medicine , neuroscience , endocrinology , phosphorylation , biology , biochemistry , in vitro , stereochemistry , nuclear magnetic resonance spectroscopy
Postspike after‐hyperpolarizations (AHPs) control the excitability of neurons and are important in shaping firing patterns. The duration of some of these events extends to tens of seconds and they can render neurons inexcitable for much of their time course. While consensus is strong that the medium duration (< 1 s AHPs are mediated by the opening of small conductance Ca 2+ ‐activated K + channels, the K + channels mediating slow AHPs (> 5 s in a subset of enteric (AH) neurons) have an intermediate unit conductance (IK Ca ). Using whole‐cell and excised‐patch recording, we have demonstrated that the cAMP‐protein kinase A (PKA) pathway regulates the activity of these channels. In whole‐cell mode, forskolin (0.003–1 μ m ) inhibited the current underlying the slow AHP ( I sAHP ) by 90 %, and this was partially sensitive to inhibition of PKA with internal Rp‐cAMPS (500 μ m ). Rp‐cAMPS alone increased the current following break‐in and caused a 20 mV hyperpolarization, suggesting that PKA maintains slow AHP channels in the closed state. Internal perfusion of the inhibitory peptide PKI 5–24 slightly increased the I sAHP and opposed the inhibitory action of forskolin. Internal perfusion of the catalytic subunit of PKA (PKA cat ) suppressed the I sAHP by 50 % without affecting membrane potential or action potential configuration. In inside‐out patches containing IK Ca ‐like channels, PKA cat decreased the open probability of IK Ca ‐like channels while alkaline phosphatase activated them. These results suggest that the IK Ca ‐like channels that underlie the slow AHP in myenteric AH neurons are subject to inhibition by PKA‐dependent phosphorylation and that PKA plays an integral role in their gating.