Speculations on the impact of Ca++-regulated splicing on protein and neuronal functions. (A) On the fine-tuning of the Ca++ sensitivity of ion channels (for example, the BK channels). With Ca++ sensitivities between 0 to 100 μM (top), and increasing number of different ion channels (right) available through alternative splicing, the spectrum of the Ca++ sensitivity is becoming increasingly refined with narrower intervals (suppose the Ca++ concentration intervals are even). For simplicity, only the effect of up to 1000 variant channels is shown, with more indicated by “… …”. (B) Modulation of splice variant ratios beyond cell-specific expression of a limited number of variants by cell signals such as Ca++. Shown are two splice variants expressed in a cell with n% for variant 1 and (100-n)% for variant 2 when there is no signal. This relative percentage can be shifted smoothly if varying strengths of Ca++ stimuli are applied to modulate the splicing resulting in a spectrum of variant percentages ranging from 0% to 100% for each variant. (C) Diagram of the possible contribution of Ca++/CaMK IV-regulated alternative splicing to changes in neuronal electrical properties during electrophysiological memory. Changed electrical firing during the 1st and 2nd round stimulations is indicated with a different amplitude and frequency. This change requires gene expression through CaMK IV. The control of alternative splicing of ion channels by CaMK IV to either promote or repress the inclusion of certain exons is expected to contribute to the changes in ion channel subunit compositions and therefore the firing properties.