Quantitative Measurement of Binding Sites and Washout Components for Calcium Ion in Vascular Smooth Muscle

Abstract

In a recent review article (Weiss, 1977a), a general hypothesis was developed concerning the central importance of Ca²⁺ to any comprehensive understanding of responsiveness of muscle systems to pharmacological agents. Briefly, this view was that both the qualitative and the quantitative nature of the muscle response to a given agent is directly determined by the amounts of intracellular Ca²⁺ available and this, in turn, is a direct consequence of differing Ca²⁺-binding properties of the specific cytoarchitecture present in each particular type of muscle. This is not to say that other phases of the sequence beginning with the drug-receptor interaction are not also essential. However, determination of the nature of the final response obtained is not a function of receptor activation but, rather, a result of alterations in membrane binding and permeability characteristics and, ultimately, a direct function of the intracellular Ca²⁺ level. Though this relationship exists in all types of muscle, elaboration of correlations between muscle tension and Ca²⁺ distribution and movements has not progressed as rapidly in smooth muscle as in striated muscle. The sequence of events leading from membrane excitation to muscle contraction in striated muscle has been convincingly documented (see Sandow, 1965; Bianchi, 1968) and related to clearly defined morphological structures. However, in smooth muscle anatomical structures resembling those observed in striated muscle are not as readily identified and, partly as a consequence of this, specific cellular sources and sites for Ca²⁺ cannot be delineated in a parallel fashion.