Myocardial Amino Acid Transport in the Isolated Rabbit Right Ventricular Papillary Muscle

Abstract

The amino acid analog, alpha-aminoisobutyric acid (AIB) has been used to study myocardial amino acid transport in the isolated rabbit right ventricular papillary muscle. Intracellular AIB accumulation is linear for 2 hours and reaches a plateau at 3 hours at an intracellular/extracellular concentration gradient of 3.4. Anoxia does not inhibit this process whereas simultaneous inhibition of aerobic and anaerobic metabolism inhibits AIB accumulation. Intracellular AIB accumulation follows Michealis-Menten kinetics with a Km of 6.8 X ICHM and a V max of 6.6 fjt,mo\es • ml intracellular fluid -1 • hour" 1 . Sodium ion is obligatory for the transport process whereas no absolute potassium or calcium requirement exists. Ouabain, 10~5M, inhibits AIB uptake. Myograph techniques were utilized to determine the effect on AIB accumulation of subjecting unstimulated papillary muscles to various degrees of passive stretch. Muscles incubated at any tension above zero developed a greater intracellular/extracellular fluid AIB concentration ratio than muscles incubated at zero tension. These data suggest that increased myocardial wall tension may be a mechanical stimulus capable of inducing adaptive changes in myocardial metabolism.ADDITIONAL KEY WORDS extracellular fluid space hypertrophy tension ouabain cellular volume• The heart will hypertrophy when exposed to the stress of a sustained increase in mechanical work, thus suggesting that the mechanical activity of the heart partially regulates the cellular mechanisms which determine myocardial mass. Some of the biochemical characteristics of the hypertrophied heart have been described in the intact heart following banding of the aorta and pulmonary artery, or in an overloaded perfused heart From the

The energetics of myocardial stretch. Creatine kinase flux and oxygen consumption in the noncontracting rat heart.

“…Several studies suggest that such energy needs may respond to prolonged periods of passive stretch. For example, uptake of the amino acid analog, a-aminoisobutyric acid, by isolated right ventricular papillary muscle increased by a factor of two when the muscle was stretched passively with a tension of 4.0 g, but increased incorporation of labeled phenylalanine into protein did not appear unless stretch persisted for more.than 180 minutes (Lesch et al, 1970). Isolated hearts that were perfused by the Langendorff technique showed decreased protein degradation and increased protein synthesis when they were perfused at 120 mm Hg for more than 60 minutes compared to 60 mm Hg (Gordon et al, 1984).…”

The influence of immobilization and stretch on protein turnover of rat skeletal muscle.

“…Recent studies have indicated that rates of protein degradation are inhibited while rates of protein synthesis remain unchanged, after short periods of stretching isolated muscles. In contrast to these findings other investigators have reported that protein synthesis increases upon passively stretching the levator anus or extensor digitorum longus (EDL) muscles (Buresova, Gutmann & Kliepera, 1969) and the papillary muscle of the heart (Lesch et al 1970).…”

“…Such work-induced growth appears to be independent of hormonal factors (Goldberg, 1967) and presumably allows selective growth of individual, or specific groups, of muscles when required rather than a general growth of the body's musculature. In addition to skeletal muscle, growth of uterine smooth muscle during pregnancy (Csapo, Erdos, Demattos, Grauss & Moscowitz, 1965) and the papillary muscle of the heart (Lesch, Gorlin & Sonnenblick, 1970) may be induced by stretching.…”

Myocardial Protein Synthesis in Acute Myocardial Hypoxia and Ischemia

“…Lesh et al [25] have reported that transport of «-aminoisobutyric acid into isolated non beating papillary muscle of the rabbit ventricle occurs at the same rate in oxygen and in nitrogen and that glycolysis furnishes sufficient energy to support the active uptake of this amino acid. This does not seem to be the case in liver and brain, where anoxia and cyanide inhibit the concentrative uptake of «-aminoisobutyric acid and other «-amino acids [1, 7.…”