Ca2+ Homeostasis

Excitation-contraction coupling in smooth muscle generally depends on increases in the cytoplasmic [Ca] which lead to activation of the contractile proteins. Understanding how these [Ca] signals are generated and terminated is, therefore, central to any understanding of how smooth muscle contracts and relaxes.

My research is focussed on this and involves the use of Ca-indicator dyes with microfluorimetry (allowing good time resolution) and confocal laser microscopy (giving information about the spatial distribution of the signals). Combining these techniques with voltage clamp allows simultaneous recording of relevant membrane currents (including Ca currents and Ca-activated currents) and provides for better control of experimental conditions. These approaches have allowed us to explore [Ca] changes in stomach muscle, and have indicated an important role for the intracellular stores in buffering the impact of Ca entry across the cell membrane and in regulating resting [Ca].
Confocal microscopy also allows us to investigate Ca-stores more directly, and will make it possible for intracellular [Ca] gradients to be imaged during electrical and chemical stimulation.