Diaphragm disuse reduces ca2+ uptake capacity of the sarcoplasmic reticulum. Howell, Sandra, Wen-Zhi Zhan, Gary C. Sieck. Departments of Biokinesiology and Physical Therapy, and Biomedical Engineering, University of Southern California, Los Angeles, CA; and the Departments of Anesthesiology and Physiology and Biophysics, Mayo Clinic, Rochester, MN
APStracts 3:0416A, 1996.
Chronic phrenic tetrodotoxin (TTX) blockade and phrenic denervation (DNV) of hamster diaphragm result in decreased maximum specific tension, prolonged contraction time, and improved fatigue resistance (Zhan and Sieck, J. Appl. Physiol. 72:1445-1453, 1992). An underlying increased relative contribution of type I fibers to total muscle mass appears to be consistent with, but does not completely account for, changes in contractile and fatigue properties. The present study was designed to evaluate a potential role for altered cellular Ca2+ metabolism in the adaptive response of the diaphragm to chronic disuse. An analytic method based on simulation and modeling of long -term 45Ca2+ efflux data was used to estimate Ca2+ contents (nmol Ca2+/g wet wt tissue) and exchange fluxes (nmol Ca2+/min/g) for extracellular and intracellular compartments in in vitro hamster hemidiaphragm following prolonged disuse. Three groups were compared: control (CTL, n=5), phrenic TTX blockade (TTX, n=5), and phrenic denervation (DNV, n=5). Experimental muscles were loaded with 45Ca2+ for 1 hr and efflux data collected for 8 hrs using a flow-through tissue chamber. Compartmental analysis of efflux data estimated that the Ca2+ contents and Ca2+ exchange fluxes of the largest and slowest intracellular compartment (putative longitudinal reticulum) were reduced by about one half in TTX and DNV muscle groups compared with CTL. In addition, the kinetic model predicted significant decreases in total intracellular Ca2+ and total diaphragm Ca2+ in TTX and DNV muscles. We conclude that the data support the hypothesis that the capacity of the sarcoplasmic reticulum for Ca2+ sequestration is reduced in chronic diaphragm disuse. The impact of this effect on diaphragm contractile and fatigue properties is discussed. 

Received 6 March 1995; accepted in final form 27 August 1996.
APS Manuscript Number A257-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996