Neurotransmitter amino acids potentiate current through Ca_v2.3 channels by acting as trace metal chelators. (A) Representative current traces recorded in response to the I-V protocol (V_hold = −90 mV; depolarizations to −15, −10, −5, 0, 10, and 20 mV) in a standard HEPES-buffered solution, containing 5 mM Ca²⁺ as a charge carrier, before (a) and after the addition of 200 µM Glu (b). Highlighted current traces elicited in response to 0-mV voltage step. (B) Normalized peak current I-V relationships measured in control HEPES and Glu-containing solutions. Data from each cell were fitted with GHK Eq. 1 (HEPES: V_1/2 = 19.4 ± 1.9 and k = 7.4 ± 0.2 mV; Glu: V_1/2 = 5.4 ± 2.0 and k = 5.9 ± 0.3 mV; **, P < 0.001 by paired Student’s t test for both parameters; n = 5). (C) Voltage dependence of the potentiating effect of Glu on Ca_v2.3. Ratio of peak current amplitudes (I_Glu/I_HEPES) at each potential plotted as a function of potential. (D) Potentiating effect of 200 µM Glu (n = 5), 200 µM Gly (n = 4), 100 µM DTPA (n = 11), and 10 mM Tricine (n = 8) on Ca_v2.3 currents elicited by the test pulses to −15–0 mV (***, P < 0.0001 by one-way ANOVA). (E) Time course of changes in the peak current amplitude induced by the sequential application of the indicated solutions measured at −20 mV. Note that the effect of Glu on Ca_v2.3 is abolished by coapplication of DTPA.