Molecular nature of voltage‐gated calcium channels: structure and species comparison

The progression from one to three to 10, and in some instances more, voltage‐gated calcium channels within living organisms during the course of evolution has paralleled the development of complex neuronal and signaling pathway development. Over time, the core structural elements allowing movement of calcium across the cellular membrane in a voltage‐dependent manner have been built upon through the modification of the intra‐ and extracellular regions of the calcium channel protein structure. This has allowed the flow of calcium ions to be coupled to a broad spectrum of signaling and modulatory mechanisms that interact at both the intra‐ and extracellular surfaces. Changes in splice‐variant composition also provide another layer of complexity to the repertoire of possible calcium channels. From next generation sequencing techniques it is becoming clear that much more work remains towards furthering our understanding of the regulation and complexity of splice variation within single channel subtypes. Careful analysis needs to be undertaken within specific target tissues and cell types together with temporal aspects of development and disease pathophysiology in order to confirm that the correct splice‐variant context is considered. Subfamily‐specific calcium channel variations in both vertebrates and invertebrates provide the opportunity to identify both subfamily and organism specific blockers. WIREs Membr Transp Signal 2013, 2:181–206. doi: 10.1002/wmts.91 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website .