Novel description of the large conductance Ca(2+)‐modulated K(+) channel current, BK, during an action potential from suprachiasmatic nucleus neurons

The contribution of the large conductance, Ca(2+)‐modulated, voltage‐gated K(+) channel current, I(BK), to the total current during an action potential (AP) from suprachiasmatic nucleus (SCN) neurons is described using a novel computational approach. An experimental recording of an SCN AP and the corresponding AP‐clamp recording of I(BK) from the literature were both digitized. The AP data set was applied computationally to a kinetic model of I(BK) that was based on results from a clone of the BK channel α subunit heterologolously expressed in Xenopus oocytes. The I(BK) model result during an AP was compared with the AP‐clamp recording of I(BK). The comparison suggests that a change in the intracellular Ca(2+) concentration does not have an immediate effect on BK channel kinetics. Rather, a delay of a few milliseconds may occur prior to the full effect of a change in Ca(i) (2+). As shown elsewhere, the β2 subunit of the BK channel in the SCN, which is present in the daytime along with the α subunit, shifts the BK channel activation curve leftward on the voltage axis relative to the activation curve of BK channels comprised of the α subunit alone. That shift may underlie the diurnal changes in electrical activity that occur in the SCN and it may also enhance the delay in the effect of a change in Ca(i) (2+) on BK kinetics reported here. The implication of these results for models of the AP for neurons in which BK channels are present is that an additional time dependent process may be required in the models, a process that describes the time dependence of the development of a change in the intracellular Ca(2+) concentration on BK channel gating.