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(a) Calcium release from the sarcoplasmic reticulum. (b) Calcium uptake into the sarcoplasmic reticulum.

Platelet aggregation and actions of antiplatelet drugs.^1,3 Resting platelets have specific receptors for ligands that trigger activation: epinephrine, thrombin, serotonin, collagen, adenosine diphosphate (ADP), and thromboxane A₂ (TXA₂). When activated, intracellular calcium levels elevate and the platelet expresses glycoprotein (GP) IIb/IIIa receptors that bind to strands of fibrinogen. This results in platelet aggregation. The various antiplatelet drugs inhibit aggregation by targeting specific aspects of this process.

Effects of lidocaine and articaine on viability of SH-SY5Y cells. (A) Expression of Na(V) in SH-SY5Y cells. Polymerase chain reaction gel showing cells expressed mRNA for both Na(V)1.2 and Na(V)1.7. Gels show bands of expected size from 3 cell preparations. “-1.2” and “-1.7” indicate lanes where reverse transcriptase was omitted from the mix for Na(V)1.2 and Na(V)1.7, respectively. Bars are 100 base pairs. (B) Example of images of SH-SY5Y cells loaded with the Live/Dead assay in response to various conditions. Cells treated for 5 minutes with 4% articaine or 2% lidocaine (both from the cartridge), washed, then loaded with the Live/Dead dye. Positive control of cells treated with 70% ethanol are shown on the top left, while untreated cells are shown on the right. Green, calcein indicating healthy cells; red, ethidium homodimer indicating compromised cells. Bar = 100 μM. (C) Quantification of Live/Dead levels from SH-SY5Y cells treated with lidocaine + 1 : 100,000 epinephrine or articaine + 1 : 100000 epinephrine from the cartridges used clinically. The reduced viability observed using lidocaine at full strength was not significant (Kruskal-Wallis 1-way analysis on ranks with Dunn's post hoc test). Articaine did not lead to cell death at any strength. Numbers along the abscissa axis indicate the percentage of drug, with 2% lidocaine and 4% articaine the full strength from the cartridge. Numbers along the ordinate represent the ratio of light excited at 488 nm versus 544 nm, normalized to the mean control for each set. *p < .001 methanol versus saline; n = 10. (D) Quantification of the Live/Dead levels from SH-SY5Y cells treated with pure lidocaine or articaine. Lidocaine increased the number of dead cells when used in pure powdered form at the highest concentration, while pure articaine did not alter cell survival. Numbers along the abscissa indicate the concentration in mM, with the highest levels of both drugs equal to the maximum level with the cartridge. Numbers along the ordinate represent the Live/Dead ratio normalized as in C. *p < .001 (methanol and 74 mM lidocaine), n = 18.

Neuronal responsiveness impaired by previous lidocaine treatment. (A) Typical baseline cytoplasmic Ca²⁺ levels in SH-SY5Y cells. (B) Mean levels of Ca²⁺ under baseline conditions (B, 5 mM K⁺) and after exposure to 50 mM K⁺ (HK) in cells exposed to 2% lidocaine, 4% articaine or control solution 30 minutes before measurements were made. Baseline Ca²⁺ levels show no significant difference between the 3 treatment groups. While depolarization with the high K⁺ solution significantly raised cellular Ca²⁺ levels in the control cells (*p =0.004) and those previously exposed to articaine (**p = .031), the response in cells previously exposed to 2% lidocaine was not significant, Student's t test, n = 15.