The contribution of Ca2+ signaling and Ca2+ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

Bai Y, Sanderson MJ. The contribution of Ca2+ signaling and Ca2+ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice. Am J Physiol Lung Cell Mol Physiol 296: L947-L958, 2009. First published April 3, 2009; doi: 10.1152/ajplung.90288.2008.-To determine the relative contributions of Ca2+ signaling and Ca2+ sensitivity to the contractility of airway smooth muscle cells (SMCs), we compared the contractile responses of mouse and rat airways with the lung slice technique. Airway contraction was measured by monitoring changes in airway lumen area with phase-contrast microscopy, whereas changes in intracellular calcium concentration ([Ca2+](i)) of the SMCs were recorded with laser scanning microscopy. In mice and rats, methacholine (MCh) or serotonin induced concentration-dependent airway contraction and Ca2+ oscillations in the SMCs. However, rat airways demonstrated greater contraction compared with mice, in response to agonist-induced Ca2+ oscillations of a similar frequency. Because this indicates that rat airway SMCs have a higher Ca2+ sensitivity compared with mice, we examined Ca2+ sensitivity with Ca2+-permeabilized airway SMCs in which the [Ca2+](i) was experimentally controlled. In the absence of agonists, high [Ca2+](i) induced a sustained contraction in rat airways but only a transient contraction in mouse airways. This sustained contraction of rat airways was relaxed by Y-23672, a Rho kinase inhibitor, but not affected by GF-109203X, a PKC inhibitor. The subsequent exposure of Ca2+-permeabilized airway SMCs, with high [Ca2+](i), to MCh elicited a further contraction of rat airways and initiated a sustained contraction of mouse airways, without changing the [Ca2+](i) of the SMCs. Collectively, these results indicate that airway SMCs of rats have a substantially higher innate Ca2+ sensitivity than mice and that this strongly influences the transduction of the frequency of Ca2+ oscillations into the contractility of airway SMCs.