This study investigated the mechanisms underlying the propagation of cytoplasmic @entity460 waves and the genesis of systolic @entity141 alternans in cardiac myocytes lacking transverse tubules (t-tubules). These correspond to atrial cells of either small mammals or large mammals that have lost their t-tubules due to disease-induced structural remodeling (e.g., @entity955 ). A mathematical model was developed for a cluster of @entity8452 receptors distributed on the cross section of a cell that was divided into 13 elements with a spatial resolution of 2  m. Due to the absence of t-tubules, L-type @entity141 channels were only located in the peripheral elements close to the cell-membrane surface and produced @entity141 signals that propagated toward central elements by triggering successive @entity141 -induced @entity141 release (CICR) via @entity141 diffusion between adjacent elements. Under control conditions, the @entity141 signals did not fully propagate to the central region of the cell. However, with modulation of several factors responsible for @entity141 handling, such as the L-type @entity141 channels ( @entity141 influx), SERCA pumps (sarcoplasmic reticulum (SR) @entity141 uptake), and @entity8452 receptors (SR @entity141 release), @entity141 wave propagation to the center of the cell could occur. These simulation results are consistent with previous experimental data from atrial cells of small mammals. The model further reveals that spatially functional heterogeneity in @entity141 diffusion within the cell produced a steep relationship between the SR @entity141 content and the cytoplasmic @entity141 concentration. This played an important role in the genesis of @entity141 alternans that were more obvious in central than in peripheral elements. Possible association between the occurrence of @entity141 alternans and the model parameters of @entity141 handling was comprehensively explored in a wide range of one- and two-parameter spaces. In  addition, the model revealed a spontaneous second @entity141 release in response to a single voltage stimulus pulse with SR @entity141 overloading and augmented @entity141 influx. This study provides what to our knowledge are new insights into the genesis of @entity141 alternans and spontaneous second @entity141 release in cardiac myocytes that lack t-tubules.

Mechanisms by which cytoplasmic XXXX wave propagation and alternans are generated in cardiac atrial myocytes lacking T-tubules-insights from a simulation study.

@entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity955 :: ('MESH:D001281', 'Disease') :: ['atrial fibrillation'] @entity8452 :: ('MESH:D012433', 'Chemical') :: ['ryanodine'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium']
@entity460 :: (MESH:D002118,Chemical) :: ['calcium']
