Modulation of dihydropyridine receptors in vascular smooth muscle cells by membrane potential and cell proliferation

Academic Article

Abstract

  • We have studied binding of isradipine to A7r5 vascular smooth muscle cells as a function of membrane potential and cell proliferation. Consistent with a voltage-modulated receptor model, two classes of binding sites were detected in confluent cultures: high-affinity sites under depolarizing (50 mM K+) conditions (Kd = 45 ± 3 pM), and lower affinity sites under resting (5 mM K+) conditions (Kd = 181 ± 20 pM). However, proliferating cells also displayed the high-affinity state at rest (Kd = 29 ± 9 pM) in addition to a low-affinity site (Kd = 869 ± 383 pM). Analysis of dissociation rates also revealed two receptor classes during proliferation. Proliferating cells showed a single class of high-affinity sites (Kd = 39 ± 6 pM) when depolarized, similar to confluent cells. Receptor density in confluent monolayers increased from 15 ± 3 fmol/106 cells at 5 days to 72 ± 6 fmol/106 cells after 10 days. These results suggest (i) that some L-type Ca2+ channels are spontaneously active in proliferating vascular smooth muscle cells, but require depolarization to activate in a confluent monolayer, and (ii) that the density of dihydropyridine receptors increases after a monolayer becomes confluent. © 1994.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Ruiz-Velasco V; Mayer MB; Inscho EW; Hymel LJ
  • Start Page

  • 311
  • End Page

  • 318
  • Volume

  • 268
  • Issue

  • 3