Modulation by PKA of the Hyperpolarization-activated Current (Ih) in Cultured Rat Olfactory Receptor Neurons

Modulation by PKA of the Hyperpolarization-activated Current (Ih) in Cultured Rat Olfactory... The hyperpolarization-activated Ih channel is modulated by neurotransmitters acting through the cAMP messenger system. In rat olfactory receptor neurons (ORNs), dopamine, by inhibition of adenylyl cyclase, shifts the voltage of half-maximal activation (V1/2) of Ih to more negative potentials and decreases Ih maximal relative conductance. Whether these effects result from a phosphorylation-dependent mechanism is unclear. Therefore, we used whole-cell patch-clamp recording techniques to study cAMP-dependent phosphorylation via PKA on Ih in rat ORNs. General protein kinase inhibition (50 nM K252a) produced a hyperpolarizing shift in Ih V1/2 and decreased Ih maximal conductance. Specific inhibition of PKA with H-89 (500 nM) also shifted the V1/2 of Ih to more negative potentials, and, in some cells, decreased Ih maximal conductance. PKA-mediated phosphorylation (cBIMPS, 50 mM) shifted Ih V1/2 more positive, modulated the kinetics of Ih channel activation and increased Ih peak current amplitude. Internal perfusion of the catalytic subunit of PKA (84 nM) also shifted Ih V1/2 positive and this shift was blocked by co-perfusion with PKI (50 nM). These results show that in rat ORNs, the voltage dependence of Ih activation can be modulated by PKA-dependent phosphorylation. We also show that PKA and other protein kinases may be involved in the regulation of Ih maximal conductance. Our findings suggest that changes in the phosphorylation state of ORNs may affect resting properties as well as modulate odor sensitivity. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Modulation by PKA of the Hyperpolarization-activated Current (Ih) in Cultured Rat Olfactory Receptor Neurons

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Publisher
Springer-Verlag
Copyright
Copyright © 2002 by Springer-Verlag New York Inc.
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-001-0178-y
Publisher site
See Article on Publisher Site

Abstract

The hyperpolarization-activated Ih channel is modulated by neurotransmitters acting through the cAMP messenger system. In rat olfactory receptor neurons (ORNs), dopamine, by inhibition of adenylyl cyclase, shifts the voltage of half-maximal activation (V1/2) of Ih to more negative potentials and decreases Ih maximal relative conductance. Whether these effects result from a phosphorylation-dependent mechanism is unclear. Therefore, we used whole-cell patch-clamp recording techniques to study cAMP-dependent phosphorylation via PKA on Ih in rat ORNs. General protein kinase inhibition (50 nM K252a) produced a hyperpolarizing shift in Ih V1/2 and decreased Ih maximal conductance. Specific inhibition of PKA with H-89 (500 nM) also shifted the V1/2 of Ih to more negative potentials, and, in some cells, decreased Ih maximal conductance. PKA-mediated phosphorylation (cBIMPS, 50 mM) shifted Ih V1/2 more positive, modulated the kinetics of Ih channel activation and increased Ih peak current amplitude. Internal perfusion of the catalytic subunit of PKA (84 nM) also shifted Ih V1/2 positive and this shift was blocked by co-perfusion with PKI (50 nM). These results show that in rat ORNs, the voltage dependence of Ih activation can be modulated by PKA-dependent phosphorylation. We also show that PKA and other protein kinases may be involved in the regulation of Ih maximal conductance. Our findings suggest that changes in the phosphorylation state of ORNs may affect resting properties as well as modulate odor sensitivity.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Jul 1, 2002

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