Developmental downregulation of low-voltage-activated Ca²⁺ channels in Cajal-Retzius cells of the mouse visual cortex

Abstract

Cajal-Retzius (CR) cells have been demonstrated to fulfil an important secretory function in the developing neocortex. On the other hand, the contribution of CR cell electrical activity during cortex development is still unclear. Using the whole-cell patch-clamp technique, we studied low-voltage-activated (LVA) Ca²⁺ channels in CR cells in the layer I of the mouse visual cortex. CR cells were found to display a transient Ca²⁺ current (I_T) in response to a depolarization step from −100 mV to −40 mV. I_T showed: (i) typical for LVA Ca²⁺ channels voltage dependence of activation (half-activation at −55 mV) and inactivation (half-inactivation at −76 mV); (ii) fast activation and inactivation kinetics, with time constants of 1.4 and 28 ms, respectively, at −40 mV; (iii) fast recovery from steady-state inactivation (time constant: 290 ms); (iv) a complete block by 1 µm mibefradil; and (v) a partial block (to 55%) by 100 µm Ni²⁺. The density of I_T dramatically decreased between postnatal day (P) 1 and P9. Immunostaining demonstrated the presence and postnatal downregulation of the α_1G-subunit of LVA Ca²⁺ channels in CR cells. Experiments performed in the current-clamp mode revealed that mibefradil delayed an action potential generation in response to a suprathreshold depolarizing current at P1, but not at P8–9. We suggest that LVA Ca²⁺ channels might influence CR cell excitability during the first postnatal week and thereby contribute to the shaping of synaptic connectivity in the neocortical layer I.