Search for author "Zhilin Qu"

Multiscale behaviors. A, Stochastic protein behavior. Single-channel recording of an L-type Ca channel from a cardiac myocyte, during successive voltage-clamp pulses from −40 to 0 mV, showing different behaviors on each sweep. Downward deflections indicate channel openings. B, Regular cell behavior. Integrated behavior of stochastic ion channel network creates a dependably regular AP and Ca transient from beat-to-beat. C, Pathological tissue behavior. In addition to coordinating the normal heart beat, wave propagation at the tissue level also permits reentry which can cause life-threatening arrhythmias.Show Less

A, Graded Ca release. SR Ca release flux (black) tracks the amplitude of the L-type Ca current (red) during voltage clamps to different membrane voltages (Vm) in a rabbit ventricular myocyte, reproduced by the couplon network model (right). Reproduced from Altamirano and Bers24 with permission from the American Heart Association. B, Voltage-dependent EC coupling gain. Left, EC coupling gain, defined as the ratio of SR Ca release to the L-type Ca current amplitude, is higher at less-depolarized voltages in experimental data from rabbit ventricular myocytes. Reproduced from Altamirano and Bers24 with permission from the American Heart Association. Right, The steep decline in gain is reproduced better in the couplon network model, when the couplons are coupled (solid symbols) than when uncoupled (open symbols). C, Steep SR fractional release–load relationship. Left, The fraction of SR Ca released increases steeply as the SR load increases in a rabbit ventricular myocyte. Reproduced from Shannon et al22 with permission from Elsevier. Right, The steepness is more accurately reproduced by the couplon network model (right) when the couplons are coupled (solid symbols) than when uncoupled (open symbols). D, Ca alternans. During rapid pacing with a fixed AP waveform (black), the Ca transient (red) alternates between large and small on successive beats in a patch-clamped rabbit ventricular myocyte (top), reproduced by the couplon network model (bottom panels). Second panel shows alternans of the global Ca transient and SR Ca content during pacing with a fixed-voltage waveform. Third and fourth panels show 2 representative couplons in the network, exhibiting irregular activations instead of alternans. Fifth and sixth panels show the spatial patterns of Ca release from couplons during alternans on 4 successive beats. Note that when the 2 small beats or 2 large beats are compared to each other, the spatial patterns differ, indicating the macroscopic alternans is not accompanied by microscopic alternans. Reproduced from Rovetti et al8 with permission from the American Heart Association.Show Less

Ca alternans. A, Ca alternans attributable to CICR waves on alternate beats, elicited by successive voltage-clamp pulses from −40 to −20 mV in a ventricular myocyte (top; reproduced from Diaz et al6 with permission from the American Heart Association) and the couplon network model (bottom). Line scans with spatial position vertically and time horizontally are shown. Note that the Ca waves initiate at different locations on the first and third beats. B, Dissociation between SR Ca release and load during alternans. When heart rate was decreased (left panels), Ca alternans resolved in a patch-clamped rabbit ventricular myocyte (top left; reproduced from Picht et al31 with permission from the American Heart Association) and the 3 R model (bottom left; reproduced from Rovetti et al8 with permission from the American Heart Association). Left panels show that SR load (diastolic [Ca]SR) was lower during regular beating than during alternans, even though the SR depletion was larger than during the small Ca transient.Show Less

Electrical restitution and alternans. A, APD and CV restitution curves. As DI decreases, APD shortens and CV slows. B, Positive and negative Cai-APD coupling. See text. C, Arrhythmogenic spatially discordant APD alternans. In region a, APD alternans has a long-short pattern, whereas region b has a short–long pattern, separated by a nodal line without alternans. If a PVC (*) occurs in the short APD region, it can block as it propagates across the nodal line into in the long APD region, while propagating laterally until the long APD region recovers, initiating figure-eight reentry.Show Less