Fig. 9: Proposed model by which KV2.1 macro-clusters disruption eliminates sex-specific differences in Ca2+ influx via CaV1.2 channels.

Enhanced S590A phosphorylation (yellow circles labeled with a “P”) of KV2.1 channels (red) in KV2.1WT female myocytes increases KV2.1 macro-clustering concomitant with larger CaV1.2 channel clusters (blue) and increased CaV1.2 channel activity (red trace). KV2.1WT male and S590A mutant myocytes exhibit decreased or no S590 phosphorylation compared to KV2.1WT female myocytes, disrupting the formation of KV2.1 macro-clusters. CaV1.2 channel clusters are smaller and exhibit less activity.