CK inhibition accelerates transcytosolic energy signaling during rapid workload steps in isolated rabbit hearts

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 276; no. 1; p. H134
• Main Authors: Harrison, Glenn J, van Wijhe, Michiel H, de Groot, Bas, Dijk, Francina J, van Beek, Johannes H G M
• Format: Journal Article
• Language: English
• Published: United States 01.01.1999
• Subjects: energy transduction; adenosine 5′-diphosphate diffusion; oxygen consumption; contractile reserve
• ISSN: 1522-1539

The effect of graded creatine kinase (CK) inhibition on the response time of mitochondrial O consumption to dynamic workload jumps ( t ) was studied in isolated rabbit hearts. Tyrode-perfused hearts ( n = 7/group) were exposed to 15 min of 0, 0.1, 0.2, or 0.4 mM iodoacetamide (IA) (CK activity = 100, 14, 6, and 3%, respectively). Pretreatment t was similar across groups at 6.5 ± 0.5 s (mean ± SE). The increase observed over time in control hearts (33 ± 8%) was progressively reversed to 16 ± 6, -20 ± 6 ( P< 0.01 vs. control), and -46 ± 6 ( P < 0.01 vs. control) % in the 0.1, 0.2 and 0.4 mM IA groups, respectively. The faster response times occurred without reductions in mitochondrial oxidative capacity (assessed in vitro) or myocardial O consumption of the whole heart during workload steps. Isovolumic contractile function assessed as rate-pressure product (RPP) and contractile reserve (increase in RPP during heart rate steps) were significantly reduced by IA. We conclude that CK in the myofibrils and/or cytosol does not speed up transfer of the energy-related signal to the mitochondria but rather acts as an energetic buffer, effectively slowing the stimulus between myofibrils/ion pumps and oxidative phosphorylation. This argues against the existence of an obligatory creatine phosphate energy shuttle, because CK is effectively bypassed.