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

摘要: 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) forskolin modulate Ih primary afferents by shifting activation curve depolarizing direction increasing maximum amplitude. 3. The cAMP analogues, RP-cAMP-S (an inhibitor protein kinase A (PKA)) SP-cAMP-S activator PKA), both shifted more depolarized potentials occluded effects forskolin. These results suggest that is modulated a direct action analogues. 4. Superfusion other cyclic nucleotide analogues (8-Br-cAMP, 8-(4-chlorophenylthio)-cAMP 8-Br-cGMP) mimicked actions PGE2, but dibutyryl cGMP, 5'-AMP adenosine had no effect on Ih. 8-Br-cAMP 8-Br-cGMP similar concentration response profiles, suggesting has little selectivity. 5. peptide (PKI), catalytic subunit PKA (C subunit) phosphatase inhibitors (microcystin okadaic acid) modulation 6. indicate regulated nucleotides sensory neurons. Positive regulation prostaglandins produced during inflammation may lead depolarization facilitation repetitive activity, thus contribute sensitization painful stimuli.