Modulation of the hyperpolarization-activated current (I-h) by cyclic nucleotides in guinea-pig primary afferent neurons
Modulation of the hyperpolarization-activated current (I-h) by cyclic nucleotides in guinea-pig primary afferent neurons
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DOI：
10.1113/jphysiol.1996.sp021292
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发表时间：
1996-04-01
影响因子：
5.5
通讯作者：
Williams, JT
中科院分区：
文献类型：
--
作者：
Ingram, SL;Williams, JT
1.采用全细胞膜片钳技术记录离体培养的豚鼠结状核和三叉神经节神经元，研究超极化激活电流（I-h）的第二信使机制.前列腺素E（2）（PGE（2））和forskolin通过使激活曲线向去极化方向移动和增加最大振幅来调节初级传入的I-h. cAMP类似物RP-cAMP-S（蛋白激酶A（PKA）的抑制剂）和SP-cAMP-S（PKA的激活剂）均使I-h的激活曲线向更高的去极化电位移动，并阻断forskolin的作用。这些结果表明，I-h是由cAMP类似物的直接作用调节的。灌流其它环核苷酸类似物（8-Br-cAMP、8-（4-氯苯硫基）-cAMP和8-Br-cGMP）可模拟forskolin和PGE（2）的作用，但二丁酰cGMP、5 ′-AMP和腺苷对I-h无影响。8-Br-cAMP和8-Br-cGMP具有相似的浓度响应曲线，提示I-h对核苷酸的选择性很小.抑制肽（PKI）、PKA的催化亚基（C亚基）和磷酸酶抑制剂（微囊藻毒素和冈田酸）对毛喉素调节I-h没有影响。这些结果表明，在感觉神经元中，I-h受到环核苷酸的调节。炎症过程中产生的野牡丹素对I-h的正性调节可能导致去极化和促进重复活动，从而有助于对疼痛刺激的敏感化。
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 (I-h) modulation.2. Prostaglandin E(2) (PGE(2)) and forskolin modulate I-h 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 I-h to more depolarized potentials and occluded the effects of forskolin. These results suggest that I-h 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 PGE(2), but dibutyryl cGMP, 5'-AMP and adenosine had no effect on I-h. 8-Br-cAMP and 8-Br-cGMP had similar concentration response profiles, suggesting that I-h 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 I-h.6. These results indicate that I-h is regulated by cyclic nucleotides in sensory neurons. Positive regulation of I-h by prostaglandins produced during inflammation may lead to depolarization and facilitation of repetitive activity, and thus contribute to sensitization to painful stimuli.