Abstract
Outward current oscillations associated with transient membrane hyperpolarizations were induced in murine macrophage polykaryons by membrane depolarization in the absence of external Na+. Oscillations corresponded to a cyclic activation of Ca(2+)-dependent K+ currents (IKCa) probably correlated with variations in intracellular Ca2+ concentration. Addition of external Na+ (8 mM) immediately abolished the outward current oscillations, suggesting that the absence of the cation is necessary not only for their induction but also for their maintenance. Oscillations were completely blocked by nisoldipine. Ruthenium red and ryanodine reduced the number of outward current cycles in each episode, whereas quercetin prolonged the hyperpolarization 2- to 15-fold. Neither low molecular weight heparin nor the absence of a Na+ gradient across the membrane had any influence on oscillations. The evidence suggests that Ca2+ entry through a pathway sensitive to Ca2+ channel blockers is elicited by membrane depolarization in Na(+)-free medium and is essential to initiate oscillations, which are also dependent on the cyclic release of Ca2+ from intracellular Ca(2+)-sensitive stores; Ca2+ ATPase acts by reducing intracellular Ca2+, thus allowing slow deactivation of IKCa. Evidence is presented that neither a Na+/Ca2+ antiporter nor Ca2+ release from IP3-sensitive Ca2+ stores participate directly in the mechanism of oscillation.
Highlights
Transmembrane potential oscillations have been encountered in many cell types, including both excitable and non-excitable cells
We examined the genesis and modulation of the depolarization-induced outward K+ current oscillations in macrophage polykaryons and evaluated the role of the various mechanisms involved in intracellular Ca2+ homeostasis, including calcium channels, Na+/Ca2+ antiporter, Ca2+ ATPase and intracellular Ca2+ stores
We investigated the participation of various processes related to cytoplasmic Ca2+ homeostasis in the regulation of the outward potassium current oscillations activated by depolarization in Na+free saline
Summary
Transmembrane potential oscillations have been encountered in many cell types, including both excitable and non-excitable cells They are often associated with oscillations in intracellular Ca2+ concentrations that activate Ca2+-dependent K+ currents (IKCa) [1,2,3] and can be useful as an alternative to direct measurement of intracellular Ca2+concentration [4,5]. In non-excitable cells, Ca2+ oscillations are generated by different mechanisms: cyclic Ca2+ release from intracellular sources, either by inositol triphosphate (IP3) as in Xenopus oocytes and megakaryocytes [6,7,8], or by cytoplasmic Ca2+-activated mechanisms as in hamster eggs [9], or Ca2+ entry-dependent oscillations as in endothelial cells [3]. The response of the same cell to repeated exposure to the same agonist can be remarkably similar [1]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
