PMCA, SERCA and Na, K ATPase Alpha Isoforms and Ca2+ Homeostasis in Smooth Muscle Evidence from Gene-Altered Mice
Year: 2003
Type: article
Abstract: Maintenance and modulation of [Ca2+], is of central importance in regulation of vascular contractility.Key to setting steady states are the plasma membrane (PMCA) and sarco (endo) plasmic reticulum Ca2+ ATPase (SERCA) pumps, the SERCA modulator phospholamban (PLB), and Na, K ATPase coupled to the Na-Ca exchanger.The relative roles played by each in Ca2+ homeostasis is unknown, and further complicated by the existence of isoforms (PMCA1-4, SERCA1-3, Na,K ATPase alphal-4 and multiple potential splice variants of each).Interestingly, further variety can be introduced by specialized localization, such as the unique subsarcolemmal localizations of the alphal and alphal Na, K ATPase isoforms.Gene-targeted and transgenic mouse models provide unique models to evaluate the role played by these pumps in regulation of vascular smooth contractility, and include SERCA2,3, PLB, PMCA1 & 4 and Na, K ATPase alphal & 2 Isoform knockouts.Modulation of SERCA by PLB can be a major factor in contractility in both tonic and phasic smooth muscles, as shown by PLB-KO or mice expressing the PLB transgene in smooth muscles.In contrast, little change in contractility in the SERCA2 +/-was found Contractility in PMCAl+/-was elevated whereas in PMCA4-/-paradoxically, little change was noted.Alpha 2-/-Na, K ATPase KOs showed increased contractility, but not alphal +/-, which has similar decreases in total Na, K ATPase.LCa2+]i measurements suggest a general pattern in which minor changes in Ca2+ homeostasis are reflected in contractility.However, major disruptions lead to altered Ca2+-sensitivity, such that the stimulus-force relations are maintained.Thus it appears that Ca2+ homeostasis and Ca2+ sensitivity of the contractile apparatus are intertwined and coordinately regulated.
Institution: University of Cincinnati
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2035312381