Inactivation mode of sodium channels defines the different maximal firing rates of conventional versus atypical midbrain dopamine neurons
Fig 2
Atypical maximum frequency is limited by recovery from fast inactivation, but some long-term inactivation is needed for hysteresis.
A. No long-term inactivation. A1. Weak triangular ramp (50 pA peak relative to baseline) in atypical model with no long-term inactivation (see panel A3) does not induce DP block. Time course of occupancy in the fast inactivated state, blue trace, bottom. A2. Strong triangular current ramp (600 pA) in atypical model with no long-term inactivation induces DP block with little hysteresis, such that spiking is reinstated on the down branch (membrane potential, upper trace). The fraction of channels in the fast inactivated state saturates (blue trace at bottom). A3. For I1-I2 = 0, the long-term inactivated state is effectively removed from the Markov model. B. Long-term inactivation added. The maximal I1-I2 transition rate is 26.7 s-1 as in Fig 1. B1. Response of atypical model (voltage trace, top) with long-term inactivation to a weak triangular current ramp (50 pA). B2. A stronger triangular ramp current (100 pA) induces depolarization block at a lower current amplitude than in A2. Bottom traces in each panel: time course of occupancy in I1 (blue) and I2 (green) states and their sum (red trace). B3. The green arrow in the Markov model shows which parameter was changed between A and B. Ramp currents are calibrated such that the initial hyperpolarizing step is identical for all cells (-25 pA) but the peak current relative to the hyperpolarized baseline is variable. Parameters are the ‘atypical’ values given in Table 1.