Frank-Starling Relationship

Abstract

Konhilas et al6 have provided a much needed quantitative test of the idea that changes in filament lattice spacing account for the increase in Ca2+ sensitivity of myocardial force at long lengths. Their results imply that length-dependent changes in lattice spacing are not the only factor, and possibly not the principal factor, determining the length dependence of Ca2+ sensitivity thought to underlie the Frank-Starling relationship. At the same time, their findings do not suggest a mechanism to explain length-dependent activation in myocardium. Possibilities include effects of stretch on thick filament structure or crossbridge disposition via the elastic protein titin or length-dependent changes in cooperative processes that modulate activation, but such ideas need to be explored. In this regard, the x-ray methods used by Konhilas et al6 have extraordinary potential for elucidating effects of stretch on the structure of the myofilaments, but such experiments will be even more difficult than those discussed here. The emerging complexity of mechanisms underlying the Frank-Starling relationship recalls the words of A.V. Hill: "There are more things in heaven and earth, Horatio, ... and even in... [heart] muscles" (page 22).