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

XB-ART-54231

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

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

Clay JR .

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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.

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Species referenced: Xenopus
Genes referenced: kcnma1 sri

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	Figure 1. Top panel: AP from figure 12 of Jackson et al. (2004). The 0 mV level corresponds to the top of the bar labeled 50 mV. This waveform was used to obtain the AP‐clamp 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 Figure 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 Equations (1), (2), (3) for IBK. Left panel: Currents elicited from the model with 6 msec duration voltage clamp steps from +20 to +110 mV, with 10 mV increments between each step. Initial value of n(t) in Equation 2 at the beginning of each step was n = 0. Right panel: Deactivation currents for an initial value of n = 1 with V = −10, −30, −50, and −70 mV.
	Figure 4. Relative conduction for IBK as a function of Cas. The data points with error bars were taken from Figure 5B from Cui et al. (1997). The curves correspond to n∞ = αBK/(αBK + βBK) with αBK and βBK given in Equation 3 and αCa = 0.03/[1 + (Log{Cas/Cao})2], βCa = 0.04/[1 + (Log{Cas/Cao})2], and VCa = 147–75 log[Cas/Cao] mV.
	Figure 5. Time constants of IBK for three different levels of Cas. The data points are from Cui et al. (1997). Specifically, the results for Cas = 0.84, 1.7, and 10.2 μmol/L were taken from Figure 2A and 3A, 2B and 3B, and 2C and 3C, respectively (Cui et al. 1997), the right‐hand panel in each case. The lines correspond to τBK = 1/[αBK(V) +βBK(V)] with αBK(V) and βBK(V) as given in Equation 3 in the text.
	Figure 6. Relative maximum time constants as a function of Cai 2+ (Cas) from Cui et al. (1997) and Cox (2014). The results for Cui et al. (1997) correspond to the maximum values of the curves in Figure 5: Cas = 0.84 μmol/L, 5.3 msec; Cas = 1.7 μmol/L, 5.0 msec; Cas = 10.2 μmol/L, 3.1 msec. The results from Cox (2014) were taken from Figure 1D of that report: Cas = 0.9 μmol/L, 5.8 msec; Cas = 2.4 μmol/L, 4.2 msec; Cas = 7.8 μmol/L, 1.9 msec, and Cas = 22 μmol/L, 1.5 msec. These results were normalized relative to the Cas = 0.9 μmol/L result from Cox (2014). The curve corresponds to 1/[1 + (Log{Cas/Cao})2] with Cao = 1 μmol/L.

References [+] :

Augustine, Local calcium signaling in neurons. 2003, Pubmed