Modeling of BK channel properties in rat chromaffin cells

Abstract

Activation and inactivation properties of the large conductance Ca²⁺-and voltage-activated K⁺ channel (BK_i channel) in rat chromaffin cells were modeled based on the experimental data provided by M. Prakriya et al., J. Neurosci. 16: 4344, 1996) and J. P. Ding et al., Biophys. J. 82: 2448, 2002). The BK_i channel model was tested in simulation by incorporating it into a previously developed chromaffin cell model which comprises mechanisms of Ca²⁺ influx through voltage-activated Ca²⁺ channels, Ca²⁺ diffusion and extrusion. The BK_i channel model is designed to sense the submembrane [Ca²⁺]_i increase with two overlapped domains; one is derived from a rapidly formed Ca²⁺ microdomain around a pore of open Ca²⁺ channel positioned at 50-60 nm distance from individual BK_i channel, and the other develops slowly in a cell-averaged fashion as the result of buffered intracellular Ca²⁺ diffusion. Calculations with the model appropriately reproduced characteristic details shown in experimental records, which are as follows: 1) BK_i current profiles induced by imposing a two-step voltage clamp, first pulses to -9 mV for varying durations to load the cell with various amounts of Ca²⁺ followed by a test pulse to +81 mV; 2) Distinct influences of EDTA and BAPTA on the BK_i current profiles during the two-step voltage pulses due to different Ca²⁺-binding rates of the buffers; 3) A change in the profile of action potential. with inhibition of BK_i channel; 4) Role of BK_i channels on the generation of repetitive firing. Thus, the proposed BK_i channel model may be useful as a mechanism implemented in chromaffin cell model. [J Physiol Sci. 2007;57 Suppl:S229]