Fig 2. Simulated currents of voltage-gated calcium channels EGL1-9, UNC-2, and CCA-1.

Calcium currents can be classified according to their activation voltage level: EGL19 and UNC2 currents activate at high membrane potential (V > ∼ − 40 mV), while CCA1 currents start to activate at low voltages (V ∼ −70 mV) [15, 20, 36, 37, 75]. Stimulation protocol (sketched in panel D) consists in 10 mV voltage steps ranging from -80 mV to 40 mV. Each step lasts 200 ms, and is applied from a holding potential V_h = −80 mV. The reversal potential for calcium is V_Ca = 60 mV. EGL19, UNC2, and CCA1 currents are given by Eqs B5, B10, and B14 in S1 File, respectively, in which ${\overline{g}}_{\text{EGL}19}=200\text{nS}$, ${\overline{g}}_{\text{UNC}2}=23\text{nS}$, and ${\overline{g}}_{\text{CCA}1}=25\text{nS}$ (conductance values are chosen to match the currents of reference experimental data). The currents are expressed in nA, depending on the experimental data used as reference. A) EGL19 current. Experimental data for steady-state activation and inactivation variables from [15] and for activation and inactivation time constants from [36]. EGL19 current activates rapidly (${\tau }_{m_{\text{EGL}19}}\sim 6\text{ms}$ at 0 mV) at high voltage (V > −30 mV, see S3 Fig). The voltage dependence of the activation time constant is described by the sum of two Gaussian functions with shifted centers (Eq B2 in S1 File and S3 Fig), as in [76]. The steady-state inactivation function has a U-shape, with a minimum of about 0.5 at 0 mV (Eq B3 in S1 File and S3 Fig). The inactivation time constant voltage dependence is described by the sum of two sigmoids (Eq B4 in S1 File and S3 Fig), as in [76]. B) UNC2 current. Experimental data for steady-state activation and inactivation curves from [37], and for activation and inactivation time constants from [38] and [39], respectively. UNC2 current starts to activate at voltages slightly lower than in the case of EGL19 (V_0.5 ∼ −10 mV and ∼6 mV for UNC2 and EGL19, respectively), with a steady-state activation function steeper than EGL19 (k_a ∼ 4 mV and ∼8 mV for UNC2 and EGL19, respectively) (Eq B6 in S1 File and S3 Fig). The current shows fast activation with time constant voltage dependence described by a bell-shaped curve (Eq B7 in S1 File and S3 Fig) with a maximum value ${\tau }_{m_{\text{UNC}2}}=0.8\text{ms}$ at around -10 mV. Inactivation time constant is described by two sigmoids with ∼90 ms $<{\tau }_{h_{\text{UNC}2}}<\sim 150\text{ms}$ (Eq B9 in S1 File, and S3 Fig). C) CCA1 current. Experimental data from [40]. CCA1 current exhibits a fast activation with a time constant ${\tau }_{m_{\text{CCA}1}}<10\text{ms}$ for V > −40 mV, followed by an inactivation with a time constant ${\tau }_{h_{\text{CCA}1}}\sim 20\text{ms}$ for V > −30 mV. The current activates at more negative potentials than UNC2 and EGL19 currents (V_0.5 ∼ −60 mV) (Eq B11 in S1 File and S3 Fig), and the steady-state activation and inactivation curves overlap between -70 mV and -30 mV giving rise to a sustained inward current, named window current (S3 Fig). D) Stimulation protocol. 10 mV voltage steps, range -80 mV to 40 mV, step duration 200 ms.