PubMed · 9656050
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V M Vizgirda, S D Kim. 1998. Malignant hyperthermia.. https://pubmed.ncbi.nlm.nih.gov/9656050/
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Previous descriptions by whole-cell patch clamping of the calcium-inhibited non-selective cation channel (NSC1) in the plasma membrane of Saccharomyces cerevisiae (H. Bihler, C.L. Slayman, A. Bertl, FEBS Lett. 432 (1998); S.K. Roberts, M. Fischer, G.K. Dixon, D.Sanders, J. Bacteriol. 181 (1999)) suggested that this inwardly rectifying pathway could relieve the growth inhibition normally imposed on yeast by disruption of its potassium transporters, Trk1p and Trk2p. Now, demonstration of multiple parallel effects produced by various agonists and antagonists on both NSC1 currents and growth (of trk1 Delta trk2 Delta strains), has identified this non-selective cation pathway as the primary low-affinity uptake route for potassium ions in yeast. Factors which suppress NSC1-mediated inward currents and inhibit growth of trk1 Delta trk2 Delta cells include (i) elevating extracellular calcium over the range of 10 microM-10 mM, (ii) lowering extracellular pH over the range 7.5-4, (iii) blockade of NSC1 by hygromycin B, and (iv) to a lesser extent by TEA(+). Growth of trk1 Delta trk2 Delta cells is also inhibited by lithium and ammonium; however, these ions do not inhibit NSC1, but instead enter yeast cells via NSC1. Growth inhibition by lithium ions is probably a toxic effect, whereas growth inhibition by ammonium ions probably results from competitive inhibition, i.e. displacement of intracellular potassium by entering ammonium.
Patch-clamp recordings were performed to study the effects of three calmodulin (CaM) antagonists on the gating of intermediate calcium-activated K(+) channels (IK(Ca)) of human erythrocytes. In the cell-attached configuration, both opening frequency and open probability of IK(Ca) channels were not significantly different in control cells and in those incubated with calmidazolium, trifluoperazine or W7. IK(Ca) channels in excised membrane patches, were normally activated by the calcium bathing the cytoplasmic side in the presence of CaM antagonists, at calcium concentrations ranging from 10(-7) to 10(-3) M. The activity of IK(Ca) channels, which had been previously up-modulated by an endogenous cAMP-dependent protein kinase, was not inhibited when perfused with CaM antagonists. The results presented in this study demonstrate that calmodulin antagonists do not inhibit the activity of native IK(Ca) channels of human erythrocytes. These data are in accordance with findings on the cloned IK(Ca) indicating that calmodulin is constitutively associated with these channels.
Modulation of intracellular calcium ion concentration ((Ca2+)i) could be used to control cellular and molecular responses that are important in cell and tissue engineering. Electrical stimulation (ES) has been used to activate plasma membrane ion channels including Ca2+channels, and to induce changes in (Ca2+)i. Strong direct current (dc) ES depolarizes the membrane electrical potential (MEP) and, thereby, causes rapid increases in (Ca2+)i. Electrocoupling mechanisms that could control (Ca2+)i increases induced by modes of ES other than dc have not been elucidated, however. Here we report that 30 min of continuous exposure to a 1 or 10 Hz, 2 V/cm ES induces an (Ca2+)i increase by approximately 6-fold (baseline 25 nM) in human fibroblasts in culture. In contrast, a 100 Hz, 2 V/cm ES causes no significant (Ca2+)i increase. Either depletion of Ca2+from the extracellular medium or incubation of cells with verapamil inhibits the (Ca2+)i increase, indicating that Ca2+ influx through verapamil-sensitive Ca2+channels is required for the (Ca2+)i increase induced by oscillatory ES. More intense ES by a 1 Hz or a dc 10 V/cm electric field causes a rapid 20 to 25-fold (Ca2+)i increase. We hypothesize that selective, partial activation of Ca2+channels is likely to mediate Ca2+influx. These results suggest that optimal ES could be used to control Ca2+entry and, thereby, regulate cellular calcium homeostasis without adversely affecting cell viability.