Voltage-Dependent and Receptor-Operated Calcium Channels

Contraction of airways smooth muscle is universally accepted as being the principal component of the acute phase of airflow limitation that characterizes an asthmatic attack. It is also acknowledged that the airway structure of asthmatic subjects is abnormal. The abnormality is, in all likelihood, a consequence of the profound inflammatory processes that thicken the airway wall and promote transudation of mucus and oedema fluid into the airway lumen. Coincident with, or consequent upon, these changes there occurs an increase in airways smooth muscle mass which is hyperresponsive to a wide range of provoking stimuli. Despite detailed knowledge of these fundamental changes in airways smooth muscle and its contractile state, some of which have been recognized for a considerable period of time, it is only relatively recently that the complex molecular mechanisms underlying contraction of airways smooth muscle have begun to be unravelled. Detailed discussion of several different aspects of this subject can be found elsewhere in this series. The specific objective of this chapter is to provide a brief overview of the pharmacology of the voltage-dependent and receptor-operated calcium channels present in airways smooth muscle cells. In this context, our attention will be focussed only on those calcium channels that exist within the plasmalemmal membrane of airways smooth muscle cells and not on those calcium release channels found in the sarcoplasmic reticulum within the cells. These latter channels are dealt with elsewhere.