A Ca²⁺‐binding protein with numerous roles and uses: parvalbumin in molecular biology and physiology

Abstract

Parvalbumins (PVs) are acidic, intracellular Ca(2+)-binding proteins of low molecular weight. They are associated with several Ca(2+)-mediated cellular activities and physiological processes. It has been suggested that PV might function as a "Ca2+ shuttle" transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus, PV may contribute to the performance of rapid, phasic movements by accelerating the contraction-relaxation cycle of fast-twitch muscle fibers. Interestingly, PVs promote the generation of power stroke in fish by speeding up the rate of relaxation and thus provide impetus to attain maximal sustainable speeds. However, immunological monitoring of diverse tissues demonstrated that PVs are also present in non-muscle cells. The axoplasmic transport and various intracellular secretory mechanisms including the endocrine secretions seem to be controlled by the Ca2+ regulation machinery. Any defect in the Ca2+ handling apparatus may cause several clinical problems; for instance, PV deficiency alters the neuronal activity, a key mechanism leading to epileptic seizures. Moreover, atypical relaxation of the heart results in diastolic dysfunction, which is a major cause of heart failure predominantly among the aged people. PV may offer a unique potential to correct defective relaxation in energetically compromised failing hearts through PV gene transfer. Consequently, PV gene transfer may present a new therapeutic approach to correct cellular disturbances in Ca2+ signaling pathways of diseased organs. Hence, PVs appear to be amazingly useful candidate proteins regulating a variety of cellular functions through action on Ca2+ flux management.

Differences in locomotor performance between individuals: importance of parvalbumin, calcium handling and metabolism

“…Importantly, the efficacy of Ca 2+ re-sequestration into the sarcoplasmic reticulum depends strongly on parvalbumin (Arif, 2008). Parvalbumin is an intracellular Ca 2+ binding protein that is involved in numerous cellular processes by regulating Ca 2+ concentration spatially and temporally (Arif, 2008).…”

“…Muscle relaxation is facilitated by the activity of the sarcoplasmic reticulum Ca 2+ -ATPase (SERCA) that pumps Ca 2+ back into the sarcoplasmic reticulum (Berchtold et al, 2000). The rate of Ca 2+ resequestration, and thereby muscle relaxation, is enhanced by parvalbumin, which initially binds Ca 2+ before it is transported into the sarcoplasmic reticulum by SERCA (Arif, 2008).…”

“…With respect to Ca 2+ handling proteins, we predicted (iv) that inhibition of DHPR will affect sustained performance negatively, while inhibition of RyR will decrease sprint performance (Hirata et al, 2007;James et al, 2011). Lastly, we tested the hypothesis that (v) increased parvalbumin expression will enhance sprint and sustained locomotion (Arif, 2008;James et al, 2011).…”

Parvalbumin Gene Transfer Impairs Skeletal Muscle Contractility in Old Mice

“…PV is a high-affinity, slow buffer of Ca 2 + , whose expression decreases in rat fasttwitch skeletal muscle with aging (by 63% in EDL muscles from 8-month-old rats compared with 24-month-old rats) (Cai et al, 2001). Since PV contributes significantly to relaxation rates in fast muscles (Carroll et al, 1997), restoration of PV levels has been proposed as a potential therapeutic strategy to improve Ca 2 + handling mechanisms and thus help maintain muscle function during aging (Arif, 2009). We therefore investigated whether increased expression of PV would improve muscle function in aged mice.…”

“…Based on the observation that aging is accompanied by a large (63%) decrease in PV protein abundance in rat EDL muscles (Cai et al, 2001), restoration of PV levels in skeletal muscles could potentially enhance force production in old mice. PV overexpression has therefore been proposed as a potential intervention for sarcopenia (Arif, 2009).…”