Figure 8.

Model for receptor specificity of Ca²⁺ signals and AKAP79/150 actions in SCG neurons. M channel, and L-type and N-type Ca²⁺ channels are all regulated by G_q/11-coupled muscarinic M₁ receptors, which activate PLCβ, hydrolyzing PIP₂ into IP₃ and DAG. Depletion of PIP₂ is primarily responsible for the suppression of M-, N-, and L-current. M channels are also regulated by PLC-linked bradykinin B₂ and purinergic P2Y receptors, which induce significant cytoplasmic Ca²⁺ signals as a result of their spatial colocalization with IP₃ receptors. The Ca²⁺ signals activate CaM to suppress M-channel activity. Similar to M₁ receptors, angiotensin II AT₁ receptors suppress I_M by PIP₂ depletion. Another mechanism that inhibits I_M activity is AKAP79/150-mediated PKC phosphorylation activated by DAG, which is only involved in M₁ and AT₁ receptor modulation. The data in this paper suggest two distinct microdomains regulating M-channel activity, as shown here. In addition to the already identified microdomain that contains B₂/P2Y receptors in the plasma membrane and IP₃ receptors on the ER (light aqua), our data suggest a novel microdomain including KCNQ2/3 channels, AKAP79/150, PKC, and M₁/AT₁ receptors (light yellow). As for Ca_V1.2, AKAP79/150 is also involved in the PKA regulation of Ca_V1.3 channels, by anchoring PKA and CaN to the channels, but is not involved in G_q/11 action (light purple).