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Modulation of Ion Channel Activity in Vascular Muscle Cells by Neuropeptide Y.

出版	Université d'Ottawa / University of Ottawa, 1995
URL	http://books.google.com.hk/books?id=IKXVzwEACAAJ&hl=&source=gbs_api

註釋Neuropeptide Y (NPY) is a 36 amino acid peptide that is co-stored and co-released with noradrenaline from perivascular sympathetic nerves. In the present project, I tested the hypothesis that the vasopressor effect of NPY is related to its modulation of ion channel activities. The effects of NPY on Ca$\sp{2+}$-channel currents in freshly isolated vascular smooth muscle cells (VSMC) from the rat tail artery were studied with the perforated-patch recording technique. At a testing potential of +10 mV, the amplitude of inward current was increased by 46% in the presence of NPY 150 nM. The effects of NPY on both Ca$\sp{2+}$ current amplitude and steady-state activation were much weaker compared to the dihydropyridine agonist Bay K 8644. Unlike Bay K 8644 which shifted steady-state inactivation curve toward less positive membrane potential by 14.3 mV, NPY had no signifiant effect on steady-state inactivation of the current. A synergistic action between NPY and Bay K 8644 was observed as the combined effect of NPY and Bay K 8644 was larger than the sum of NPY and Bay K 8644 alone. The effects of NPY on the Ca$\sp{2+}$-activated K$\sp+$ channel (K$\sb{(Ca)}$) in VSMCs from the rat tail artery were also studied by whole-cell and single channel recording technique. NPY did not affect the open times or current amplitude, but increased significantly the short (from 0.49 to 0.58 ms) and long (from 441 to 728 ms) close times. An inhibition of K$\sb{(Ca)}$ channels was also observed in cell-attached patches when NPY was applied in the bath solution, indicating involvement of diffusible second messenger. The effect of NPY on K$\sb{(Ca)}$ channels was ATP-dependent. Tyrosine kinase inhibitors (genistein, lavendustin A, and tyrphostin A25) by themselves potentiated K$\sb{(Ca)}$ channel currents in a dose-dependent manner. At a testing potential of +30 mV and in the presence of genistein 15 $\mu$M, whole-cell current amplitude of K$\sb{(Ca)}$ increased by 143%. Similarly, single channel open probability increased by 120%. The potentiating effect of genistein on K$\sb{(Ca)}$ channels was ATP-dependent. Daidzein, an inactive analogue of genistein had no effect on K$\sb{(Ca)}.$ It is concluded that NPY potentiates vasoconstriction by a synergistic effect on C$\sp{2+}$ and K$\sb{(Ca)}$ channels in VSMCs. NPY can promote Ca$\sp{2+}$ entry by increasing Ca$\sp{2+}$ channel activity. Inhibition of K$\sb{(Ca)}$ channel would further increase the influx of C$\sp{2+}$ by promoting membrane depolarization and/or prolonging the duration of action potentials. It is also concluded that the effect of NPY on K$\sb{(Ca)}$-channel is mediated by a phosphorylation-dependent pathway, probably involving tyrosine phosphorylation. (Abstract shortened by UMI.).