Appendix B discusses and compares patch clamp model equations
In this notebook, we take a detailed look at the Rs compensation and slow capacitance transient cancellation scheme in figures 18 and 19 of Sigworth 1995a, and re-derive the equations found in [REF-TO-PREPRINT-WITH-SUPERCHARGING].
First, we name the voltage after the Tsc block Vest. To find an equation, we detransform the transfer function:
Tsc=A2R2C2s+1Looking back a few pages, we see that C2 is fixed, but R2 is chosen so that R2C2≈RsCm. Translating to our own notation, and ignoring the true electronic implementation, we write
R2C2=R∗sC∗mSimilarly, A2 was chosen so that A2Ci≈Cm, where Ci is the fixed capacitance used for slow transient cancellation. Although this may be a seperate estimate in practice, we will simplify by writing
A2Ci=C∗mGoing back to the transfer function, we find
Tsc=A2R∗sC∗ms+1→Vest+R∗sC∗m˙Vest=A2V′cfor ˙Vest=A2V′c−VestR∗sC∗m
In words, Vest is A2 times larger than V′c, and lags behind it with a time constant set by our estimates of Rs and Cm.
To find the voltage V′c we write the equation for the αRssCi block, using "β" instead of Sigworth's "α" and "R∗s" instead of "Rs":
V′c=Vc+βR∗sCi˙Vest=Vc+βR∗sCiA2V′c−VestR∗sC∗m(1−β)V′c=Vc−βCiC∗mVestV′c=Vc−βCiC∗mVest(1−β)Substituting this into the equation for ˙Vest we find
R∗sC∗m˙Vest=A2V′c−Vest(1−β)R∗sC∗m˙Vest=A2Vc−βA2CiC∗mVest−(1−β)Vest=A2Vc−(β+1−β)Vestfor ˙Vest=A2Vc−Vest(1−β)R∗sC∗m
In words, Vest is A2 times larger than Vc, and lags behind it with a time constant set by our estimates of the membrane capacitance and the uncompensated fraction of series resistance (1−β)R∗s.
As a result, the term fed back into V′c is βR∗sC∗m˙Vest which can be understood as βR∗sC∗m˙V′c-with-lag.
Slow transient cancellation is implemented by feeding ˙Vest into a capacitor Ci, leading to a term
ISC=A2Ci˙Vest=C∗m˙VestThe original series resistance compensation takes the updated command potential as input:
˙Vref=V′c+αR∗sIobs−VrefτsumWe can omit the "implementation details" involving A2 to write:
Although we used V′c in the derivation of ˙Vest, it only appears in the equation for Vref in the final model, and so we can simplify further by writing
Vref=Vc+αR∗sIobs+βR∗sC∗m˙VestCorrection-PredictionA schematic for this set-up is shown below
A schematic showing series resistance prediction and correction and separate pathways for fast and slow capacitance correction.