Action Potential Heterogeneity in Murine Sinoatrial Node Myocytes

Abstract

Sinoatrial node myocytes (SAMs) act as cardiac pacemakers by generating spontaneous action potentials (APs). SAMs are characterized by the expression of the “funny current” (If) that contributes to the spontaneous diastolic depolarization phase of the sinoatrial AP. SAMs exhibit a large heterogeneity of morphological and electrophysiological properties. However, limited information is available about the intrinsic variability in AP waveforms in SAMs. In this study, we co-recorded APs and If from acutely isolated SAMs from mice using voltage and current clamp recordings in the same cells. We refined the definitions of commonly used AP waveform parameters to document the heterogeneity of APs in both perforated patch (PP) and whole-cell (WC) recordings. These definitions were then implemented in an open-source data analysis program (“paramAP”) written in Python 3 using NumPy, SciPy, and Matplotlib. ParamAP was utilized to characterize APs from more than 100 SAMs. Correlation analysis was used to evaluate relationships among AP waveform parameters and to identify parameters that are strongly correlated with If and AP firing rate. Furthermore, we document time-dependent changes in AP waveform parameters during both PP and WC recordings. In summary, paramAP is a powerful tool to help standardize AP waveform analysis and parameter definitions in murine SAMs. Our data suggest that commonly-held assumptions about sinoatrial node APs should be extended to accommodate a wider range of AP waveforms. In addition, the time-dependent changes in AP waveform parameters should be considered when comparing data from different studies.