Substance P Regulates I h via a NK-1 Receptor in Vagal Sensory Neurons of the Ferret
| Autor: | Daniel Weinreich, M. Samir Jafri |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Patch-Clamp Techniques Physiology Action Potentials Substance P Sensory system Membrane Potentials chemistry.chemical_compound Neurokinin-1 Receptor Antagonists Piperidines Cations Internal medicine medicine Animals Neurons Afferent Receptor Communication Ion Transport business.industry General Neuroscience Ferrets Vagus Nerve Receptors Neurokinin-1 Endocrinology chemistry Benzamides Nodose Ganglion business Ion Channel Gating |
| Zdroj: | Journal of Neurophysiology. 79:769-777 |
| ISSN: | 1522-1598 0022-3077 |
| DOI: | 10.1152/jn.1998.79.2.769 |
| Popis: | Jafri, M. Samir and Daniel Weinreich. Substance P regulates I h via a NK-1 receptor in vagal sensory neurons of the ferret. J. Neurophysiol. 79: 769–777, 1998. Substance P (SP) hyperpolarizes ∼80% of ferret vagal sensory neurons (nodose ganglion neurons) via NK-1 receptor-mediated activation of a potassium current ( I K). A depolarizing current activated by membrane hyperpolarization could minimize the SP-induced hyperpolarization. Such a current exists in 65% of the nodose neurons ( n = 264). In this study, we examine this current and how it can interact with SP-induced membrane hyperpolarizations. This slowly developing, noninactivating inward current, designated I h, was activated maximally at about −120 mV and had a reversal potential value of −23 ± 4.4 mV ( n = 4). The time course of activation followed voltage-dependent, monoexponential kinetics. Steady-state activation curves derived from tail current analysis were well fit by a Boltzmann equation yielding a half-activation potential ( V 1/2) of−77 ± 1.5 mV and a k s value of 18 ± 0.5 ( n = 8). In the presence of 1 mM cesium, the current was completely abolished. These parameters are consistent with those derived for I h in other neurons. Substance P (200 nM) reduced the magnitude of I h elicited by membrane hyperpolarizations to about −110 mV but did not affect the magnitude of I h elicited by hyperpolarizations to more negative potentials. Tail current analysis revealed that this effect was the result of a SP-induced shift of the I h activation curve to more negative membrane potentials. The V 1/2 value for I h was shifted by −20 ± 1.4 mV in the presence of SP with no change in k s (18 ± 0.7; n = 5). The SP effect on I h, like its effect on I K, was blocked reversibly by 10 nM CP99,994, a NK-1 antagonist, and was mimicked by the NK-1 agonist Ac-[Arg6, Sar9, Met(O2)11]SP(6-11) (ASMSP; 200 nM). I h was not affected by NK-2 or NK-3 selective agonists ( n = 4 for each) nor was the effect of SP on I h reduced by an NK-2 antagonist ( n = 4). These results show that SP activates a NK-1 receptor coupled to the I h channel. Thus NK-1 receptor activation in ferret vagal afferents not only leads to membrane hyperpolarization but it also can enhance synergistically this inhibitory effect by decreasing I h. |
| Databáze: | OpenAIRE |
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