We employed two microelectrode current-clamp and voltage-clamp methods to examine the modulation of C a + + channels by norepinephrine and cyclic AMP (CAMP) in cultured astrocytes from the rat cerebral cortex. Currents owing to Cat+ channels were maximized by replacing Ca++ with Ba+ + in the extrace
Adenosine 3′∶5′-cyclic monophosphate mediates a 5-hydroxytryptamine-induced response in neonatal rat motoneurones
✍ Scribed by P. M. Larkman; J. S. Kelly; T. Takahashi
- Publisher
- Springer
- Year
- 1995
- Tongue
- English
- Weight
- 729 KB
- Volume
- 430
- Category
- Article
- ISSN
- 0031-6768
No coin nor oath required. For personal study only.
✦ Synopsis
5-Hydroxytryptamine (5-HT) is present in nerve fibres descending from the brainstem Raphe nuclei to motoneurones and its release is thought to exert excitatory actions. 5-HT, applied from the outside, directly depolarizes spinal and cranial motoneurones in slices. This action of 5-HT is mediated, in part, by an inwardly rectifying cationic current, Ih. In cardiac cells, an equivalent current, if, has been shown to be directly activated by adenosine 3': Y-cyclic monophosphate (cAMP) applied to the inside of the patch membrane. By applying the whole-cell method to thin slices of brainstem and spinal cord, we have shown that intracellularly applied cAMP and extracellularly applied dibutyryl cAMP or forskolin mimics the inward current induced by 5-HT. The selective cAMP phosphodiesterase inhibitor, Ro 20-1724, clearly prolonged the 5-HT-induced current. Maximal doses of dibutyryl cAMP or forskolin occluded the 5-HTinduced current. The broad spectrum protein kinase inhibitors 1-(5-isoquinolinesulphonyl)-2-methlypiperazine (H-7) and N-[2-(methylamino)ethyl]-5-isoquinolinesulphonamide (H-8) had no effect on the currents induced by 5-HT and forskolin. From these results, we suggest that activation of 5-HT receptors on the motoneuronal membrane stimulates formation of intracellular cAMP, thereby inducing the inward current, possibly by a direct action on Ih.
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