Figure 2. Increase of the T-type current by Zn²⁺.

(a) Analysis of I_CaT of NG108-15 cells stimulated with K⁺+Zn²⁺ (50 mM/200 μM) for 4 h, measured 1 day after stimulation. Ca²⁺ currents were recorded in the presence of Na⁺ and K⁺ current blockers (tetraethylammonium 20 mM, 4-AP 4 mM and tetrodotoxin 1 μM). Cells were depolarized from a holding potential of −80 mV to various potentials ranging from −90 to +30 mV, yielding transient, predominantly T-type Ca²⁺ currents. Representative current families elicited with the voltage protocol (upper panel) under basal conditions (left) and following increases in [Zn²⁺]_i. (b) Quantification of the peak I_CaT elicited by a step to −10 mV under the different conditions; basal: n=37 cells; K⁺: n=11 cells; K⁺+Zn²⁺: n=22 cells; t-test: **P≤0.01). (c) Current–voltage relationship of T-type currents under basal conditions and following incubation with K⁺+Zn²⁺ (filled circles basal, n=3; open circles K⁺+Zn²⁺, n=3). (d) The voltage dependence of I_CaT activation and inactivation was unaltered in cells treated with K⁺+Zn²⁺ compared with untreated controls (filled circles basal, activation n=3, inactivation n=9; open circles K⁺+Zn²⁺, activation n=3, inactivation n=6). (e) Ca²⁺ currents were elicited with a voltage step from −80 to −10 mV (upper part). Representative current traces show an increased amplitude in cells incubated with K⁺+Zn²⁺ (lower trace right) compared with cells under basal conditions (lower trace left). Representative current traces showed the potent block by 100 μM Ni²⁺, indicating involvement of Ca_V3.2 channels (grey trace). (f) Average of the transient Ca²⁺ current of all cells for control cells (basal, n=37) and cells incubated with K⁺+Zn²⁺ (n=22) display I_CaT upregulation following incubation with K⁺+Zn²⁺ (t-test: **P≤0.01). Average of the transient currents after application of 100 μM Ni²⁺ showed a large amplitude reduction in all recorded cells (−33.1±3.0 pA, n=37 versus −6.5±1.7 pA, n=9 for basal conditions and −52.2±7.8 pA, n=22 versus −10.4±3.0 pA, n=6 following incubation with K⁺+Zn²⁺).