Norepinephrine- and K+-induced Mn2+-dependent contractions and the dynamics of intracellular Mn2+ changes in dispersed smooth muscle cells from Ca2+-depleted Mn2+-loaded vas deferens of the guinea pig

The cellular mechanisms of norepinephrine (NE)-induced Mn2+-dependent contr actions were investigated in dispersed smooth muscle cells from guinea pig vas deferens by characterizing the effects of NE and K+ on cell length obse rved by videotape microscopy and on intracellular Mn2+ and Ca2+ concentrati on ([Mn2+](i) and [Ca2+](i)) observed by confocal microscopy. Both stimulan ts induced slow sustained contraction in Ca2+-depleted, Mn2+-accumulated ce lls (Mn2+-loaded cells), whereas they induced biphasic contractions in norm al cells that were neither Ca2+-depleted nor Mn2+-loaded. In both condition s, the number of cells responding to NE as well as the magnitude of NE-indu ced contractions increased in a dose-dependent manner. Contractions induced by K+ in Mn2+-loaded strip preparations were markedly smaller than those i nduced by NE. Although individual K+-induced contractions in responsive Mn2 +-loaded cells were as large as those induced by NE, a much smaller percent age 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 r eflect 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 r esponsive to NE. These results suggest that NE may increase the Mn2+ sensit ivity of contractile elements.