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

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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.