| Potassium channels serve a wide variety of functions and are found in all eukaryotic organisms, but their diversity is by far the greatest in metazoans. They are major contributors to the electrical properties of neurons and other excitable metazoan cells. Several K{dollar}sp+{dollar} channel gene families are conserved in higher triploblastic metazoans and may represent an essential set of K{dollar}sp+{dollar} channels in these complex organisms. In particular, voltage-gated K{dollar}sp+{dollar} channels in triploblasts appear to be encoded primarily by four conserved gene subfamilies, Shaker, Shal, Shab and Shaw. The goal of my dissertation research has been to better our understanding of the diversity and evolutionary origins of these voltage-gated K {dollar}sp+{dollar}channel genes. Three major contributions of this work are described in the dissertation and listed below: (1) I have discovered a novel and highly divergent family of K{dollar}sp+{dollar} channels in the ciliate protozoan Paramecium tetraurelia. Despite outward similarities between the K{dollar}sp+{dollar} currents of ciliates and metazoans, their molecular basis appears to be quite different. Shaker-like genes may have evolved after the divergence of ciliates and metazoans. (2) I have cloned and characterized homologs of Shaker and Shal from a coelenterate, the hydrozoan jellyfish Polyorchis penicillatus. The diploblastic coelenterates are the most primitive metazoans to contain nervous systems. This result suggests that much of the diversity of voltage-gated K{dollar}sp+{dollar} channels conserved in higher triploblastic metazoans was present in the first nervous systems in the last common ancestors of diploblasts and triploblasts. (3) I have discovered a novel {dollar}alpha{dollar}-like regulatory subunit that dramatically alters the inactivation rate and activation range of a Shal homolog from jellyfish. This is the first identified regulatory subunit for Shal subfamily channels, and is the first example of an {dollar}alpha{dollar}-like regulatory subunit for voltage-gated K{dollar}sp+{dollar} channels. A similar mechanism for regulating Shal may be present in Drosophila and mammals. Because Shal channels are major contributors to neuronal subthreshold A-currents in these organisms, regulation of their inactivation rates may play a role in influencing firing frequency. |
