Investigating the relaxation, following diazo-2 laser flash photolysis, of a skinned trabecular preparation from SHR hypertrophied left ventricle

Abstract

Rat models of cardiac hypertrophy are characterised by a shift in left ventricular myosin isoform from V1 (adult) to V3 (foetal), the latter being associated with a slowing of the acto-myosin ATPase rate. The aim of this study was to examine hypertrophy effects on relaxation by investigating a chemically skinned cardiac preparation from the SHR, where all the cellular membranes are rendered non-functional allowing the myofibrils to be studied in isolation. On comparison, following photolysis of the photolabile caged Ca2+ chelator diazo-2, it can be seen that the SHR fibres relax at a slower rate than their age-matched WKY counterparts. We suggest that, since the thin filament regulatory proteins seem not to be affected by cardiac hypertrophy in the rat, this result can be attributed to the shift in left ventricular myosin isoforms. The reduced relaxation rate in the SHR could be the result of a slowing of the dissociation of actin and myosin during the cross-bridge cycle. These results have previously been published in abstract form [1].

Investigating the relaxation rate, following diazo-2 photolysis, of a skinned trabecular preparation from guinea-pig hypertrophied left ventricle

“…Comparison of the behaviour of skinned trabecular preparations from hypertrophied left ventricle of the rat [15] and guinea-pig (current study) suggests that cardiac relaxation is rate-limited at the level of the actomyosin interaction.…”

“…This characteristic of cardiac hypertrophy in the guinea-pig may account for the susceptibility of this species to heart failure -assuming that the tension-generating ability continues to deteriorate with increasing hypertrophy. Rat cardiac preparations seem to maintain their ability to generate force during hypertrophy [15], with rat heart being less susceptible to failure than guinea-pig myocardium. However, rat ventricle demonstrates an adaptive shift to predominant expression of the fetal V 3 myosin isoform during hypertrophy -with a consequent change in the rate of relaxation of skinned trabeculae following photolysis of diazo-2 [15].…”

“…Rat cardiac preparations seem to maintain their ability to generate force during hypertrophy [15], with rat heart being less susceptible to failure than guinea-pig myocardium. However, rat ventricle demonstrates an adaptive shift to predominant expression of the fetal V 3 myosin isoform during hypertrophy -with a consequent change in the rate of relaxation of skinned trabeculae following photolysis of diazo-2 [15]. Adaptations at the level of the cellular membranes seem to be more important in the guinea-pig hypertrophied heart [35].…”

“…Thus, in the spontaneously hypertensive (SHR) rat, marked changes in relaxation rate are observed in the de-membranated preparation and here are directly attributable to the shift from the V1 to the V3 myosin isoform [15].…”

“…A useful comparison can be made to the very different situation that is characteristic of rat cardiac hypertrophy [15], in an attempt to elucidate the degree to which changes in specific myofibrillar proteins participate in the modifications of myocardial function characteristic of left ventricular hypertrophy. Thus, in the spontaneously hypertensive (SHR) rat, marked changes in relaxation rate are observed in the de-membranated preparation and here are directly attributable to the shift from the V1 to the V3 myosin isoform [15].…”