A 5-HT_7 Receptor-mediated Depolarization in the Anterodorsal Thalamus. II. Involvement of the Hyperpolarization-Activated Current I_h

摘要

Previous studies have shown that 5-hydroxytryptamine (5-Hn can modulate the hyperpolarization-activated nonselective cat- ion current (Ih) to elicit a membrane depolarization in neurons. However, the receptor subtype involved in this response re- mains controversial. In the accompanying study, we have iden- tified a 5-HT 7 receptor-mediated depolarization in the an- terodorsal nucleus of the thalamus (ADn). In the present study, we have examined the possible role of Ih in mediating this 5-HT 7 receptor-mediated depolarization. We used the blind tight-seal patch clamp technique to examine the ability of 5-HT to modulate Ih in the ADn. We found that 5-HT induced a shift in the voltage dependence of Ih to more depolarized potentials. The pharmacology of the receptor mediating this effect was consistent with that of a 5-HT 7 receptor. Since the 5-HT 7 re- ceptor is coupled positively to adenyl ate cyclase, we examined the cAMP dependence of the 5-HT -induced modulation of Ih. Intracellular addition of cAMP mimicked and occluded the 5-HT response. Conversely, in the presence of the protein kinase inhibitors H-8 and staurosporine, ADn neurons still expressed a 5-HT -induced shift in the voltage dependence of Ih' These results suggest that 5-HT regulates Ih in the ADn through a cAMP-dependent but protein kinase A (PKA)-independent mechanism. To determine the contribution of Ih to the 5-HT 7 receptor-mediated depolarization, we used the selective Ih blocker ZD7288. This compound greatly reduced the depolar- izing response elicited by activation of 5-HT 7 receptors