Figure 4.

Schematic representation of presynaptic terminal at the α_1A −/− NMJ. (A) Calcium dependence of neurotransmission in −/− NMJ. Overall changes include a sharp drop in quantal content at [Ca²⁺]_o/[Mg²⁺]_o = 2, but little loss of quantal content at [Ca²⁺]_o/[Mg²⁺]_o < 0.2. This can be described as a uniform scaling down of m at all [Ca²⁺]_o (downward arrow), yielding the red curve, in combination with an increased sensitivity to [Ca²⁺]_o/[Mg²⁺]_o (leftward arrow). (B) Hypothetical positioning of Ca²⁺ and I_K(Ca) channels relative to other active zone structures. (Upper) WT NMJ based on description of active zone structures in frog NMJ (20), with modifications appropriate to mammalian terminals, where vesicular fusion occurs in the central zone between double rows of membrane particles (68, 69). Positioning of I_K(Ca) channels and P/Q-type channels (purple). (Lower) −/− NMJ is hypothesized to contain R-type channels (red) in at least partial substitution for P/Q-type channels (yellow), and N-type channels (blue), which are numerous, albeit farther away from Ca²⁺ sensors and vesicle release machinery. (C) Microdomains of Ca²⁺ near Ca²⁺ channels in the WT presynaptic terminal (Top), in −/− NMJ (Middle) and in −/− NMJ in the presence of Ca²⁺ chelators (Bottom). GVIA responsiveness is lost because the impact of Ca²⁺ entry through relatively distant N-type channels is blunted by exogenous cytoplasmic Ca²⁺ buffering.