TY - JOUR
T1 - Hodgkin-Huxley type ion channel characterization
T2 - an improved method of voltage clamp experiment parameter estimation
AU - Lee, Jack
AU - Smaill, Bruce
AU - Smith, Nicolas
PY - 2006/9/7
Y1 - 2006/9/7
N2 - The Hodgkin-Huxley formalism for quantitative characterization of ionic channels is widely used in cellular electrophysiological models. Model parameters for these individual channels are determined from voltage clamp experiments and usually involve the assumption that inactivation process occurs on a time scale which is infinitely slow compared to the activation process. This work shows that such an assumption may lead to appreciable errors under certain physiological conditions and proposes a new numerical approach to interpret voltage clamp experiment results. In simulated experimental protocols the new method was shown to exhibit superior accuracy compared to the traditional least squares fitting methods. With noiseless input data the error in gating variables and time constants was less than 1%, whereas the traditional methods generated upwards of 10% error and predicted incorrect gating kinetics. A sensitivity analysis showed that the new method could tolerate up to approximately 15% perturbation in the input data without unstably amplifying error in the solution. This method could also assist in designing more efficient experimental protocols, since all channel parameters (gating variables, time constants and maximum conductance) could be determined from a single voltage step.
AB - The Hodgkin-Huxley formalism for quantitative characterization of ionic channels is widely used in cellular electrophysiological models. Model parameters for these individual channels are determined from voltage clamp experiments and usually involve the assumption that inactivation process occurs on a time scale which is infinitely slow compared to the activation process. This work shows that such an assumption may lead to appreciable errors under certain physiological conditions and proposes a new numerical approach to interpret voltage clamp experiment results. In simulated experimental protocols the new method was shown to exhibit superior accuracy compared to the traditional least squares fitting methods. With noiseless input data the error in gating variables and time constants was less than 1%, whereas the traditional methods generated upwards of 10% error and predicted incorrect gating kinetics. A sensitivity analysis showed that the new method could tolerate up to approximately 15% perturbation in the input data without unstably amplifying error in the solution. This method could also assist in designing more efficient experimental protocols, since all channel parameters (gating variables, time constants and maximum conductance) could be determined from a single voltage step.
U2 - 10.1016/j.jtbi.2006.02.006
DO - 10.1016/j.jtbi.2006.02.006
M3 - Article
C2 - 16563440
SN - 0022-5193
VL - 242
SP - 123
EP - 134
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
IS - 1
ER -