Figure 2.

Homeostatic/adaptive changes in the soma of Purkinje cells (PC) caused by malfunctioning or elimination of Ca²⁺-signaling toolkit component(s); regulation by the Ca²⁺ homeostasome. (A) A detailed situation is depicted for wild-type mice. Increases in [Ca²⁺]_i (red arrows) result from influx via Ca_V2.1 (P/Q) channels or release from internal stores (light blue) via the IP₃ receptor. IP₃ is generated by the activation of metabotropic glutamate receptors (mGluR). Ca²⁺ removal systems (blue arrows) include PMCA and NCX in the plasma membrane, SERCA pumps, and mitochondria (green). Identified Ca²⁺-signaling toolkit components including organelles, which are up- or down-regulated, are marked in yellow and magenta, respectively. (B) In PV^−/−, PC subplasmalemmal mitochondria are increased, while ER volume directly underneath the plasma membrane is decreased. (C) In addition to the changes observed in PV^−/−, in PC lacking both, PV and CB-D28k the auxiliary Ca_vβ2a subunit of Ca_V2.1 (P/Q), is decreased, leading to increased voltage-dependent inactivation of P-type currents. Model studies indicate an up-regulation of Ca²⁺ extrusion systems, possibly PMCA. (D) In PMCA2^−/− PC, expression of mGluR1 and of IP₃ receptor type 1 (IP3R1), responsible for the Ca²⁺ release from ER stores, is decreased. Also, the cytosolic Ca²⁺ buffering capacity mediated by CB-D28k is decreased. (E) In leaner mice PC that are characterized by strongly attenuated Ca_v2.1 Ca²⁺ channel function, the rapid Ca²⁺ buffering/sequestering capacity is reduced: PV and CB-D28k are down-regulated and (subplasmalemmal) ER is decreased/impaired, leading to reduced Ca²⁺ uptake.