Proposed model for the local control of TRPV4 channels in arterial myocytes. (A) In this model, a subpopulation of Ca_V1.2 and TRPV4 channels is associated with AKAP150. This anchoring protein targets PKCα to the sarcolemma of arterial myocytes. Under basal conditions, TRPV4 sparklet activity is very low. Cytosolic Ca²⁺ is largely controlled by Ca²⁺ influx via voltage-gated Ca_V1.2 channels. (B) An increase in AngII levels activates G_q-coupled receptors, increasing cytosolic DAG and IP₃ levels. DAG activates AKAP150-anchored PKCα. Upon activation, PKCα can phosphorylate nearby TRPV4 and Ca_V1.2 channels, which increases the open probability of these channels. The opening of TRPV4 channels results in the production of large sparklets. Indeed, the total Ca²⁺ influx during a TRPV4 sparklets is ∼100-fold higher than during a Ca_V1.2 sparklet. However, the overall activity of Ca_V1.2 channels is much higher than that of TRPV4 channels. This limits TRPV4 sparklets to the regulation of local [Ca²⁺]_i. A key feature of the proposed model is that AKAP150 and TRPV4 channels are mobile and could interact dynamically. Thus, the distance separating these proteins could change over time depending on physiological conditions. Accordingly, the location of TRPV4 sparklet activity could change over time depending on the proximity and activity of AKAP150-associated PKCα to these channels.