Peter Joseph Kilfoil II

RESEARCH TOPICS

Project 1- “Modulation of insulin secretion by voltage gated potassium channel subunit Kvbeta2”

Voltage-gated potassium channels (Kv) are responsible for action potential repolarization in all excitable cells, including neurons, myocytes and neuroendocrine cells.  The function of the Kv channels can be modulated by the presence of ancillary subunits which bind at their intracellular domain, such as the Kvβ subunits.  These Kvβ proteins have been shown to assist in the maturation of Kv channels in the ER, aid in their transport to the plasma membrane and to alter their gating kinetics and voltage sensitivity.  I have shown through biochemical techniques that Kvβ2 appears to be highly expressed in the pancreatic islets, and have shown that under certain conditions, insulin secretion is enhanced in mice lacking the Kvβ2 gene.  As Kvβ2 is an ion channel regulator, I use the patch-clamp technique to investigate the mechanism(s) by which it is affecting insulin release.

Project 2-“Alterations in cardiomyocyte electrophysiology in response to exposure to highly reactive aldehyde species”

In this side project, I investigated alterations in voltage-gated sodium channel gating in mouse cardiomyocytes brought about by exposure to the toxic aldehyde acrolein.  Through my findings, our research group was able to identify a possible mechanism by which this reactive aldehyde causes cardiomyocyte death- By increasing window current through the sodium channel, intracellular sodium accumulation appears to cause reversal of the sodium/calcium exchanger, resulting in reverse mode operation of this transporter, causing calcium overload, hypercontracture and ultimately cardiomyocyte death.

Project 3- “The role of Kvbeta2 in cardiac ion channel distribution and ventricular repolarization.”

While Kvbeta2 expression is greatest in the brain and neuroendocrine tissues, we have also detected its expression in the heart.  I am investigating its function in the heart using a variety of approaches, including patch clamp electrophysiology to measure cardiac repolarizing currents and action potential waveforms, telemetric ECG implants to monitor untethered and unstressed cardiac rhythms, histology, immunohistochemistry, and catheterized intracardiac pacing.

Skills developed while working in the Bhatnagar lab:

Patch clamp electrophysiology, ECG analysis, rodent survival surgery, biochemistry techniques, microscopy, immunohistochemistry, cell and tissue culture

Thesis Committee

  1. Dr. Aruni Bhatnagar, Dept. of Medicine (Mentor)
  2. Dr. Daniel Conklin, Dept. of Physiology
  3. Dr. Ronald Gregg, Dept. of Biochemistry and Molecular Biology
  4. Dr. Barbara Clark, Dept. of Biochemistry and Molecular Biology
  5. Dr. Alan Cheng, Dept. of Biochemistry and Molecular Biology

Publications

  1. Kilfoil PJ, Tipparaju SM, Barski OA, Bhatnagar A.Regulation of ion channels by pyridine nucleotides. Circ Res. 2013 Feb 15;112(4):721-41
  2. Tipparaju SM, Li XP, Kilfoil PJ, Xue B, Uversky VN, Bhatnagar A, Barski OA.  Interactions between the C-terminus of Kv1.5 and Kvβ regulate pyridine nucleotide-dependent changes in channel gating. Pflugers Arch. 2012 Jun;463(6):799-818

For recent publications, check PubMed Author Search

    Memberships

    1. American Heart Association
    2. Biophysical Society
    3. Kentucky Academy of Science