Model of Cav3 calcium channel domain and interaction with KCa1.1 channels.

<p>A calcium diffusion model is used to simulate the interaction between a Cav3 calcium source and a KCa1.1 channel located within its nanodomain (20 nm). Cav3.2 and KCa1.1 properties are based on reported values in the presence of physiological levels of [Ca]_o. <i>A,</i> Activation curves for the KCa1.1 model based on the increase of [Ca]_i when 1, 2, 4, or 8 Cav3 channels are positioned within 20 nm (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061844#s2" target="_blank">Methods</a>). A single Cav3 channel causes no activation of a KCa1.1 channel below −30 mV and only minimal activation at high voltages. Activation of KCa1.1 at low voltages (−50 mV) is only attained with 4 or 8 Cav3 channels. <i>B,</i> Activation time courses during voltage steps as in (<i>A</i>) for models with either 1 or 4 Cav3 channels positioned within 20 nm of KCa1.1. KCa1.1 activation is transient, tracking the Cav3-mediated calcium influx, but with much higher probability when 4 Cav3 channels contribute. <i>C, D,</i> Schematic diagrams of a proposed model for Cav3 activation of KCa1.1 channels. In the case of a single Cav3 channel (<i>C</i>) a small calcium domain provides only a low probability of generating the increase in [Ca]_i necessary to activate KCa1.1 channels. By comparison, summation of calcium domains generated by several neighboring Cav3/KCa1.1 channel complexes (<i>D</i>) is sufficient to activate KCa1.1. Such a contribution of more distant Cav3 channels would then be consistent with the EGTA sensitivity observed in our experiments.