The Effects of Non-Identifiability on Testing for Detailed Balance in Aggregated Markov Models for Ion-Channel Gating

AbstractAggregated Markov models are a widely used tool to model patch clamp data measured from single ion channels. These channels must obey the principle of detailed balance in thermodynamic equilibrium; otherwise, the channel is driven by an external source of energy. We investigate the power of a likelihood ratio test for detailed balance for a number of data points which is in the order of magnitude of patch clamp experiments. We show that for certain models with nearly equal dwell times, a test for detailed balance suffers from a loss of power to detect violations of detailed balance which is due to the non-identifiability of the transition rates for models with equal dwell times