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From 2005 to 2006, I worked on a 2-hour documentary entitled "Exploring Time" that aired on Discovery Science Channel. You can visit the show's website and see more clips here: www.exploringtime.org. I worked with a team of artists and scientists from across the US to produce a number of animated sequences about the way modern science has changed our perception of time. We used animation to illustrate and discuss natural cycles too fast or too slow for the human eye to see. The above clip is one of several I made for the documentary.

One part of the show focused on proteins called ion channels in heart cells as they relate to heart failure. Below is a description of my research process. As a heart beats, an electrical signal called an action potential is propagated along the surface of each cell. This signal is conducted chemically as sodium, calcium, and potassium ions pass through small channels embedded in the cell membrane.

The above illustration shows the molecular structure of an individual ion channel and a simplified representation of the cell membrane as a circuit.

The diagram above describes the voltage across a cell membrane during an action potential: the numbers identify various "phases" of the cellular action potential, including a spike in potential as the cell fires, a recovery/refractory phase, and a return to resting potential, where the cell is again ready to fire.


Note: image taken from the article "Phase 2 reentry as a mechanism of initiation of circus movement reentry in canine epicardium exposed to simulated ischemia"

The diagram above illustrates a phenomenon known as "Phase 2 reentry." Phase two refers to the refractory phase of the action potential, where the cell is supposed to be inactive, or recovering from a recent contraction. This diagram shows the cardiac myocyte membrane potential at four adjacent sites in a dog's heart. The measurements were taken simultaneously.

Phase Two reentry can be a mechanism for "circus movement" reentry, which may lead to tachycardia (high heart rate), arrhythmia, and possibly a heart attack. As you can see in the figure, exposure to ischemia (blood deprivation) results in loss of phase two at sites 3 and 4 but not at sites 1 and 2. A patch of tissue on the right side still recovering from an action potential can re-excite of the left side via a phase 2 reentry mechanism (beat "a" and schematic a). The extra beat generated by phase 2 reentry then initiates a run of tachycardia that is sustained for 4 additional cycles via a typical circus movement reentry. The proposed reentrant path is shown in schematic b. Note that phase 2 reentry provides an activation front perpendicular to that of the basic beat.

This image shows the phases of a human heartbeat, which takes about 1 second total. The irregular heartbeat below shows how mistakes at the microsecond timescale can affect events at the milliseconds timescale.

Patients with a disease known as short QT Syndrome are especially prone to heart attacks. The syndrome is characterized by a short QT portion of the heartbeat, as shown above. The idea is that an altered recovery phase of the myocyte action potential shortens the length of the overall heartbeat.

The condition may be explained by a mutation in the genes KCNH2, KCNJ2, and KCNQ1. Mutations in this gene result in irregular potassium channels, altering the characteristics of cardiac myocyte action potentials. Researchers believe that a high number of mutant channels renders some heart cells less sensitive than others, possibly simulating the conditions of ischemia. The heart of someone with short QT syndrome will be much more susceptible to various kinds of reentrant waves and therefore heart attacks.


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