The muscle phenotype is the product of genome plus environmental stimuli. The family of genes that codifies the MyHC isoforms is located in two different clusters, each isoform being encoded by a separate gene. The gene corresponding to slow MyHC is located in chromosome 14, both in humans and in mice. The other genes are positioned in chromosome 17 in humans, and in chromosome 11 in mice. The transcriptional and translational mechanisms that control the expression of MyHC isoforms are not well known, although it is believed that the main regulation is dependent on mechanical signals. These signals are probably mediated by a biochemical messenger. As a general rule, fast MyHC genes seem to be expressed "by default", whereas the slow MyHC gene would be expressed as a response to changes in load.So far, few studies have analysed the in vivo regulation of MyHC gene expression in respiratory muscles. It has recently been reported that breathing against moderate levels of inspiratory resistance quickly induces an increase in the genetic expression of slow MyHC in the diaphragm. This suggests the possibility of eliciting a phenotypic adaptation of respiratory muscles using specific training protocols. Eur Respir J 1997; 10: 2404-2410 Muscles are extremely plastic, and are capable of modifying their structure to the activity they develop [1][2][3][4]. At the molecular level, muscles are composed of different structural and enzymatic elements, whose genetic expression is modulated by such activity. Myosin is one of the main structural components of the skeletal muscles, which include respiratory muscles. This myofibrillar protein ( fig. 1), essential for muscle contraction, is composed of two heavy (MyHC) and two light chains (MyLC). The MyHC (molecular weight 220 kDa) has a globular portion at one of its ends (amino-terminal part). This site is called the "head" (or S 1 ) of the molecule, and is the site of interaction with actin. This is also the site of action for the actomyosin adenosine triphosphatase (ATPase). The two MyLC (molecular weights, 17-23 kDa) are located very close to this portion, in the "neck" of the molecule. On the other side, there is an alphahelicoidal structure (carboxy-terminal part) called the "tail". Both MyHC and MyLC present different isoforms. The presence of one or another isoform conditions the acti-vity of the myosinic ATPase [5], and these two factors determine the maximum velocity of shortening, the predominant metabolism of the fibre and its resistance to fatigue [1,[6][7][8][9][10]. In this regard, those fibres containing slow MyHC isoforms present a smaller contraction velocity but higher metabolic efficiency for maintaining similar levels of tension [11]. The relationship between the MyHC composition and fibrillar function has been evidenced, not only in skeletal limb muscles but also in the diaphragm [12]. The MyLC isoforms are involved in force transduction, and, thus, in the mechanical efficiency and economy of different kinds of contraction [13]. SERIES 'CELL BIOLOGY OF RESPIRA...