Asset Details
Do you wish to reserve the book?
Delayed afterdepolarization‐induced triggered activity in cardiac purkinje cells mediated through cytosolic calcium diffusion waves
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Delayed afterdepolarization‐induced triggered activity in cardiac purkinje cells mediated through cytosolic calcium diffusion waves
Do you wish to request the book?
Delayed afterdepolarization‐induced triggered activity in cardiac purkinje cells mediated through cytosolic calcium diffusion waves
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Delayed afterdepolarization‐induced triggered activity in cardiac purkinje cells mediated through cytosolic calcium diffusion waves
2019
Overview
Cardiac Purkinje cells (PCs) are more susceptible to action potential abnormalities as compared to ventricular myocytes (VMs), which could be associated with their distinct intracellular calcium handling. We developed a detailed biophysical model of a mouse cardiac PC, which importantly reproduces the experimentally observed biphasic cytosolic calcium waves. The model includes a stochastic gating formulation for the opening and closing of ryanodine receptor (RyR) channels, simulated with a Monte Carlo method, to accurately reproduce cytosolic calcium wave propagation and the effects of spontaneous calcium release events. Simulations predict that during an action potential, smaller cytosolic calcium wavelets propagated from the sarcolemma towards the center of the cell and initiated larger magnitude cell‐wide calcium waves via a calcium‐induced‐calcium release mechanism. In the presence of RyR mutations, frequent spontaneous calcium leaks from sarcoplasmic reticulum (SR) initiated calcium waves, which upon reaching the cell periphery produced delayed afterdepolarizations (DADs) via sodium‐calcium exchanger (NCX) and T‐type calcium (ICaT) channel activation. In the presence of isoproterenol‐mediated effects, DADs induced triggered activity by reactivation of fast sodium channels. Based on our model, we found that the activation of either L‐type calcium channels (ICaL), ICaT, sodium‐potassium exchanger (INaK) or NCX is sufficient for occurrence of triggered activity; however, a partial blockade of ICaT or INaK is essential for its successful termination. Our modeling study highlights valuable insights into the mechanisms of DAD‐induced triggered activity mediated via cytosolic calcium waves in cardiac PCs and may elucidate the increased arrhythmogeneity in PCs. Cardiac Purkinje cells (PCs) are more susceptible to action potential abnormalities than ventricular myocytes (VMs), which could be associated with their distinct intracellular calcium handling. We utilized a detailed biophysical model of a murine cardiac PC, capable of producing cytosolic calcium diffusion waves, to study the effects of altered calcium homeostasis in PCs. Our modeling study highlights valuable insights into the mechanisms of triggered activity mediated via cytosolic calcium waves in PCs and may elucidate the increased arrhythmogeneity in PCs.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
/ Animals
/ Calcium Channels, L-Type - metabolism
/ Calcium Channels, T-Type - metabolism
/ delayed afterdepolarizations
/ Heart
/ Mice
/ Mutation
/ Myocytes
/ Ordinary differential equations
/ Ryanodine Receptor Calcium Release Channel - metabolism
/ Sodium-Calcium Exchanger - metabolism
