DIAPHRAGM DISUSE REDUCES CA2-RETICULUM( UPTAKE CAPACITY OF SARCOPLASMIC)

Chronic phrenic tetrodotoxin (TTX) blockade and phrenic denervation (D nv) of hamster diaphragm result In decreased maximum specific tension, prolonged contraction time, and improved fatigue resistance (W. Z. Zh an and G. C. Sieck. J. Appl. Physiol. 72: 1445-1453, 1992). An underly ing increased relative contribution of type I fibers to total muscle m ass appears to be consistent with, but does not completely account fur , changes in contractile and fatigue properties. The present study was designed to evaluate a potential role for altered cellular Ca2+ metab olism in the adaptive response of the diaphragm to chronic disuse. An analytic method based on simulation and modeling of long-term Ca-45(2) efflux data was used to estimate Ca2+ contents (nmol Ca2+/g wet wt t issue) and exchange fluxes (nmol Ca2+ . min(-1) . g(-1)) for extracell ular and intracellular compartments in the in vitro hamster hemidiaphr agm after prolonged disuse. Three groups were compared: control (Con, n = 5), phrenic TTX blockade (TTX, n = 5), and phrenic denervation (Dn v, n = 5). Experimental muscles were loaded with Ca-45(2+) for 1 h, an d efflux data mere collected for 8 h by using a flow-through tissue ch amber. Compartmental analysis of efflux data estimated that the Ca2+ c ontents and Ca2+ exchange fluxes of the largest and slowest intracellu lar compartment (putative longitudinal reticulum) were reduced by simi lar to 50% in TTX and Dnv muscle groups compared with Con. In addition , the kinetic model predicted significant decreases in total intracell ular Ca2+ and total diaphragm Ca2+ in TTX and Dnv muscles. Tme conclud e that the data support the hypothesis that the capacity of the sarcop lasmic reticulum for Ca2+ sequestration is reduced in chronic diaphrag m disuse. The impact of this effect on diaphragm contractile and fatig ue properties is discussed.