Hiromi Tsunobuchi-Ushijima, Kaoru Ikoma and Yasuo Gomi
Department of Pharmacology, Faculty of Pharmaceutical Science, Kanazawa
University, Takara-machi 13-1, Kanazawa 920-0934, Japan
Abstract: The cellular mechanisms of norepinephrine (NE)-induced
Mn2+-dependent contractions were investigated in dispersed smooth
muscle cells from guinea pig vas deferens by characterizing the effects
of NE and K+ on cell length observed by videotape microscopy
and on intracellular Mn2+ and Ca2+ concentration ([Mn2+]i
and [Ca2+]i) observed by confocal microscopy. Both stimulants
induced slow sustained contraction in Ca2+-depleted, Mn2+-accumulated
cells (Mn2+-loaded cells), whereas they induced biphasic contractions
in normal cells that were neither Ca2+-depleted nor Mn2+-loaded.
In both conditions, the number of cells responding to NE as well as the
magnitude of NE-induced contractions increased in a dose-dependent manner.
Contractions induced by K+ in Mn2+-loaded strip preparations
were markedly smaller than those induced by NE. Although individual K+-induced
contractions in responsive Mn2+-loaded cells were as large as
those induced by NE, a much smaller percentage of Mn2+-loaded
cells was responsive to K+ than to NE. These results are consistent
with the idea that the contractions of strip preparations may reflect the
magnitude of the contractions of individual cells as well as the percentage
of responsive cells in the preparations. Inconsistent with the contractions,
the [Mn2+]i rise induced by K+ was larger than that
induced by NE, and the percentage of cells responsive to K+ was
larger than that responsive to NE. These results suggest that NE may increase
the Mn2+ sensitivity of contractile elements.
Keywords: Cation sensitization, Divalent cation, Vas deferens (guinea
pig), Single cell, Fura-red