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Modulation of the hyperpolarization‐activated current (Ih) by cyclic nucleotides in guinea‐pig primary afferent neurons.

Modulation of the hyperpolarization‐activated current (Ih) by cyclic nucleotides in guinea‐pig... 1. Whole‐cell patch‐clamp recordings were made from dissociated guinea‐pig nodose and trigeminal ganglion neurons in culture to study second messenger mechanisms of the hyperpolarization‐activated current (Ih) modulation. 2. Prostaglandin E2 (PGE2) and forskolin modulate Ih in primary afferents by shifting the activation curve in the depolarizing direction and increasing the maximum amplitude. 3. The cAMP analogues, RP‐cAMP‐S (an inhibitor of protein kinase A (PKA)) and SP‐cAMP‐S (an activator of PKA), both shifted the activation curve of Ih to more depolarized potentials and occluded the effects of forskolin. These results suggest that Ih is modulated by a direct action of the cAMP analogues. 4. Superfusion of other cyclic nucleotide analogues (8‐Br‐cAMP, 8‐(4‐chlorophenylthio)‐cAMP and 8‐Br‐cGMP) mimicked the actions of forskolin and PGE2, but dibutyryl cGMP, 5'‐AMP and adenosine had no effect on Ih. 8‐Br‐cAMP and 8‐Br‐cGMP had similar concentration response profiles, suggesting that Ih has little nucleotide selectivity. 5. The inhibitor peptide (PKI), the catalytic subunit of PKA (C subunit) and phosphatase inhibitors (microcystin and okadaic acid) had no effect on forskolin modulation of Ih. 6. These results indicate that Ih is regulated by cyclic nucleotides in sensory neurons. Positive regulation of Ih by prostaglandins produced during inflammation may lead to depolarization and facilitation of repetitive activity, and thus contribute to sensitization to painful stimuli. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Physiology Wiley

Modulation of the hyperpolarization‐activated current (Ih) by cyclic nucleotides in guinea‐pig primary afferent neurons.

The Journal of Physiology , Volume 492 (1) – Apr 1, 1996

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References (35)

Publisher
Wiley
Copyright
© 2014 The Physiological Society
ISSN
0022-3751
eISSN
1469-7793
DOI
10.1113/jphysiol.1996.sp021292
Publisher site
See Article on Publisher Site

Abstract

1. Whole‐cell patch‐clamp recordings were made from dissociated guinea‐pig nodose and trigeminal ganglion neurons in culture to study second messenger mechanisms of the hyperpolarization‐activated current (Ih) modulation. 2. Prostaglandin E2 (PGE2) and forskolin modulate Ih in primary afferents by shifting the activation curve in the depolarizing direction and increasing the maximum amplitude. 3. The cAMP analogues, RP‐cAMP‐S (an inhibitor of protein kinase A (PKA)) and SP‐cAMP‐S (an activator of PKA), both shifted the activation curve of Ih to more depolarized potentials and occluded the effects of forskolin. These results suggest that Ih is modulated by a direct action of the cAMP analogues. 4. Superfusion of other cyclic nucleotide analogues (8‐Br‐cAMP, 8‐(4‐chlorophenylthio)‐cAMP and 8‐Br‐cGMP) mimicked the actions of forskolin and PGE2, but dibutyryl cGMP, 5'‐AMP and adenosine had no effect on Ih. 8‐Br‐cAMP and 8‐Br‐cGMP had similar concentration response profiles, suggesting that Ih has little nucleotide selectivity. 5. The inhibitor peptide (PKI), the catalytic subunit of PKA (C subunit) and phosphatase inhibitors (microcystin and okadaic acid) had no effect on forskolin modulation of Ih. 6. These results indicate that Ih is regulated by cyclic nucleotides in sensory neurons. Positive regulation of Ih by prostaglandins produced during inflammation may lead to depolarization and facilitation of repetitive activity, and thus contribute to sensitization to painful stimuli.

Journal

The Journal of PhysiologyWiley

Published: Apr 1, 1996

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