ParamAP: Standardized Parameterization of Sinoatrial Node Myocyte Action Potentials

Abstract

Sinoatrial node myocytes act as cardiac pacemaker cells by generating spontaneous action potentials (APs). Much information is encoded in sinoatrial AP waveforms, but both the analysis and the comparison of AP parameters between studies is hindered by the lack of standardized parameter definitions and the absence of automated analysis tools. Here we introduce ParamAP, a standalone cross-platform computational tool that uses a template-free detection algorithm to automatically identify and parameterize APs from text input files. ParamAP employs a graphic user interface with automatic and user-customizable input modes, and it outputs data files in text and PDF formats. ParamAP returns a total of 16 AP waveform parameters including time intervals such as the AP duration, membrane potentials such as the maximum diastolic potential, and rates of change of the membrane potential such as the diastolic depolarization rate. ParamAP provides a robust AP detection algorithm in combination with a standardized AP parameter analysis over a wide range of AP waveforms and firing rates, owing in part to the use of an iterative algorithm for the determination of the threshold potential and the diastolic depolarization rate that is independent of the maximum upstroke velocity, a parameter that can vary significantly among sinoatrial APs. Because ParamAP is implemented in Python 3, it is also highly customizable and extensible. In conclusion, ParamAP is a powerful computational tool that facilitates quantitative analysis and enables comparison of sinoatrial APs by standardizing parameter definitions and providing an automated work flow.

Intracellular Na+ Modulates Pacemaking Activity in Murine Sinoatrial Node Myocytes: An In Silico Analysis

“…First, we adjusted the formulation of several ionic currents based on our measurements of I CaL [ 35 ], transient and steady-state outward K + currents (I to and I sus ) [ 36 ], and I f [ 37 ] ( Figure 1 A). Then, we applied a global optimization method [ 38 ] to scale selected model parameters ( Table A1 ) to match measured AP characteristics ( Figure 1 B and Table A2 ) [ 39 , 40 ]. The resulting optimized model reproduces AP waveform properties that closely resemble our experimental results ( Figure 1 C,D and Figure 2 A).…”

“…Briefly, SAMs were isolated from 2–3 months old male C58BL/6 J mice [ 73 , 74 ], and membrane currents and spontaneous APs were recorded at 35 °C in whole-cell and amphotericin perforated patch configurations, respectively [ 35 , 36 , 39 ]. AP characteristics (defined in Table A2 ) were determined for each cell from average waveforms from 5 s recording windows using the software ParamAP [ 40 ].…”

Bi-directional flow of the funny current (If) during the pacemaking cycle in murine sinoatrial node myocytes

“…30 s of stable AP firing was recorded followed by up to 2.5 min of AP firing with perfusion of 30 µM ivabradine in Tyrode’s solution. The average cell firing rate over the last 10 s of every 30 s period was calculated using ParamAP software (77).…”

Hypoglycaemia combined with mild hypokalaemia reduces the heart rate and causes abnormal pacemaker activity in a computational model of a human sinoatrial cell

“…We characterized the sinoatrial AP waveform using a set of parameters presented by Fabbri et al , and we calculated them based on the guidelines for standardization of AP parameters [ 28 ]. The following parameters were calculated: CL—cycle length of the pacemaker activity, defined as the duration between the peaks of two consecutive APs; PP—peak action potential, peak (maximum value) of the AP; APA—AP amplitude, defined as the difference between the maximum and minimum AP potentials; MDP—maximum diastolic potential preceding the PP, defined as the most negative repolarization potential; DDR—diastolic depolarization rate; DDR 100 —diastolic depolarization rate over the first 100 ms of diastolic depolarization; APD 90 —AP duration at 90% repolarization ( figure 1 ).…”