Received June 25, 2004
Revised September 3, 2004
Accepted after revision February 14, 2005

¹ Robert Wood Johnson Medical School
² Johns Hopkins University
³ Case Western Reserve University

^* To whom correspondence should be addressed. E-mail: brottoma{at}umdnj.edu.

	Abstract

Although it is well established that patients suffering from malaria experience skeletal muscle problems (contracture, aches, fatigue, weakness), detailed studies have not been performed to investigate changes in the contractile function and biochemical properties of intact and skinned skeletal muscles of mammals infected with malaria. To this end, we investigated such features in the extensor digitorium longus (EDL, fast-twitch, glyocolytic) and in the soleus (SOL, slow-twitch, oxidative) muscles from mice infected with Plasmodium berghei. We first studied maximal tetanic force (Tmax) produced by intact control and malaria infected muscles before, during and after fatigue. Triton-skinned muscle fibers were isolated from these muscles and used to determine isometric contractile features as well as a basic biochemical profile as analyzed by silver-enhanced SDS-PAGE. We found that the Tmax of intact muscles and the maximal Ca2+ activated force (Fmax) of Triton-skinned muscle fibers were reduced by ~ 50% in malarial muscles. In addition, the contractile proteins of Triton-skinned muscle fibers from malarial muscles were significantly less sensitive to Ca2+. Biochemical analysis revealed that there was a significant loss/reduction of essential contractile proteins (e.g., troponins, myosin, etc) in Triton-skinned muscle fibers from malarial muscles as compared to controls. The biochemical alterations (i.e., loss/reduction of essential contractile proteins) seem to well explain the functional modifications resolved in both intact muscles and Triton-skinned muscle fibers and may provide a suitable paradigm for the etiology of muscle symptoms associated with malaria.

Key Words: Excitation-contraction coupling, Muscle fatigue, Skinned fibre