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Characterizing the gating of voltage-dependent calcium (CaV1.2) channels


Cooperative gating is when the gating of one channel is dependent on the gating of another channel. CaV1.2 channels are encoded by CACNA1C and mediate L-type current in cardiac tissue. Since the probability of two CaV1.2 channels opening and closing in tandem is infinitesimally small, such a rare observation would strongly suggest cooperative gating behavior. Others have previously suggested that the frequency of cooperative gating increases in cells expressing a CaV1.2 channel carrying the Timothy Syndrome point mutation. Timothy Syndrome is a devastating disease characterized by arrhythmias and autism. As a result, the gating of the CaV1.2 channel is altered, and cells become inundated with the influx of calcium. Individuals with Timothy Syndrome typically have a prolonged QT interval, which can degenerate into cardiac arrest, and eventually death. To study the kinetic behavior of CaV1.2 channels, I conducted single-channel recordings from embryonic kidney cells transfected with cDNA encoding the CaV1.2 channel. Unfortunately, it's impossible to visually distinguish between the closed and inactivated state in the experimental record since they're both non-conducting. Additionally, when two channels are open - and only one closes - it's impossible to tell which channel closed, or the sequence of states through which the model passed. Using a combination of different idealization software and MATLAB, I plotted probability distributions of open and closed dwell times of the CaV1.2 channel to estimate the number of states within conducting and non-conducting conformations based on the number of exponential components. This analysis provides me with insight regarding the underlying kinetic model of the channel.


Kuksenko, Olena, "Characterizing the gating of voltage-dependent calcium (CaV1.2) channels" (2016). Summer Research Symposium. Brown Digital Repository. Brown University Library.



  • Summer Research Symposium

    Each year, Brown University showcases the research of its undergraduates at the Summer Research Symposium. More than half of the student-researchers are UTRA recipients, while others receive funding from a variety of Brown-administered and national programs and fellowships and go …