Clay JR (2017), Novel description of the large conductance Ca2+...

XB-ART-54231

Physiol Rep 2017 Nov 01;520:. doi: 10.14814/phy2.13473.

Show Gene links Show Anatomy links

Novel description of the large conductance Ca2+-modulated K+ channel current, BK, during an action potential from suprachiasmatic nucleus neurons.

Clay JR .

???displayArticle.abstract???
The contribution of the large conductance, Ca2+-modulated, voltage-gated K+ channel current, IBK, 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 IBK from the literature were both digitized. The AP data set was applied computationally to a kinetic model of IBK that was based on results from a clone of the BK channel α subunit heterologolously expressed in Xenopus oocytes. The IBK model result during an AP was compared with the AP-clamp recording of IBK The comparison suggests that a change in the intracellular Ca2+ 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 Cai2+ 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 Cai2+ 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 Ca2+ concentration on BK channel gating.

???displayArticle.pubmedLink??? 29084840
???displayArticle.pmcLink??? PMC5661234
???displayArticle.link??? Physiol Rep

Species referenced: Xenopus
Genes referenced: kcnma1 sri

???attribute.lit??? ???displayArticles.show???

	Figure 1. Top panel: AP from figure 12 of Jackson etÂ al. (2004). The 0Â mV level corresponds to the top of the bar labeled 50Â mV. This waveform was used to obtain the APâclamp recording of IBK shown in the bottom panel along with a simulation of that result (filled circles), as described in the text.
	Figure 2. Top panel: Same AP is in FigureÂ 1. Bottom panel: Calcium ion concentration adjacent to the internal surface of the membrane, referred to here as Cas, obtained using the AP in the top panel, as described in the text.
	Figure 3. Predictions of the model in EquationsÂ (1), (2), (3) for IBK. Left panel: Currents elicited from the model with 6 msec duration voltage clamp steps from +20 to +110Â mV, with 10Â mV increments between each step. Initial value of n(t) in EquationÂ 2 at the beginning of each step was nÂ =Â 0. Right panel: Deactivation currents for an initial value of nÂ =Â 1 with VÂ =Â âˆ’10, âˆ’30, âˆ’50, and âˆ’70 mV.
	Figure 4. Relative conduction for IBK as a function of Cas. The data points with error bars were taken from FigureÂ 5B from Cui etÂ al. (1997). The curves correspond to nâÂ =Â Î±BK/(Î±BKÂ +Â Î²BK) with Î±BK and Î²BK given in EquationÂ 3 and Î±CaÂ =Â 0.03/[1Â +Â (Log{Cas/Cao})2], Î²CaÂ =Â 0.04/[1Â +Â (Log{Cas/Cao})2], and VCaÂ =Â 147â75 log[Cas/Cao] mV.
	Figure 5. Time constants of IBK for three different levels of Cas. The data points are from Cui etÂ al. (1997). Specifically, the results for CasÂ =Â 0.84, 1.7, and 10.2Â Î¼mol/L were taken from FigureÂ 2A and 3A, 2B and 3B, and 2C and 3C, respectively (Cui etÂ al. 1997), the rightâhand panel in each case. The lines correspond to ÏBKÂ =Â 1/[Î±BK(V) +Î²BK(V)] with Î±BK(V) and Î²BK(V) as given in EquationÂ 3 in the text.
	Figure 6. Relative maximum time constants as a function of Cai 2+ (Cas) from Cui etÂ al. (1997) and Cox (2014). The results for Cui etÂ al. (1997) correspond to the maximum values of the curves in FigureÂ 5: CasÂ =Â 0.84Â Î¼mol/L, 5.3Â msec; CasÂ =Â 1.7Â Î¼mol/L, 5.0Â msec; CasÂ =Â 10.2Â Î¼mol/L, 3.1Â msec. The results from Cox (2014) were taken from FigureÂ 1D of that report: CasÂ =Â 0.9Â Î¼mol/L, 5.8Â msec; CasÂ =Â 2.4Â Î¼mol/L, 4.2Â msec; CasÂ =Â 7.8Â Î¼mol/L, 1.9Â msec, and CasÂ =Â 22Â Î¼mol/L, 1.5Â msec. These results were normalized relative to the CasÂ =Â 0.9Â Î¼mol/L result from Cox (2014). The curve corresponds to 1/[1Â +Â (Log{Cas/Cao})2] with Cao = 1Â Î¼mol/L.

References [+] :

Augustine, Local calcium signaling in neurons. 2003, Pubmed