Erwin F. Shibata, Ph.D.
        Associate Professor

Office: Lab: Phone: Lab: FAX: Email:

6-450 Bowen Science Building 6-431 Bowen Science Building (319) 335-7836 (319) 335-7837 (319) 335-7330 erwin-shibata@uiowa.edu

Research Interests

The primary focus in my laboratory is to understand the regulatory mechanism(s) of ion channels in excitable cells. Specifically, we are interested in the mechanism by which beta-adrenergic and muscarinic receptor agonists modulate ionic currents. Previous studies have suggested that in addition to the phosphorylation-dependent effects on ion channels, Gsalpha has an additional “direct” effect on the increase of cardiac Na current that is independent but concurrent with phosphorylation effects. Our results strongly suggest that the number of functional Na channels increases in the membrane and that these channels are in caveolae (Yarbrough et al., 2002). Caveolae are dynamic omega-shaped invaginations whose membrane fusion and fission mechanisms are virtually unknown. These channel proteins do not migrate out of the caveolar membrane domain. Na channels within the caveolae membrane become functional when the caveolae “neck” opens to establish electrical continuity between the extracellular space and the intra-caveolae compartment. Our studies focus on determining the co-localization of Na+, Ca2+, and K+ channels in caveolae and the role of Gsalpha in the regulation of caveolae neck fusion and fission.

Our animal models include enzymatically dissociated single myocytes from rabbit, rat and human hearts. We use several types of approaches to test our hypothesis. Some of these techniques include Western blot analysis, immunoprecipitation, confocal immuno-fluorescence, immuno-electron microscopy, and patch-clamping. The patch pipette voltage-clamp technique is used to determine changes in the biophysical properties of sodium, calcium and potassium currents as well as high-resolution capacitance measurements.

These studies will provide new information into the regulatory mechanism of caveolae ion channels in heart and direct new pharmacological interventions and therapeutic modalities of lethal arrhythmias.

Selected Publications

1. Lu, T., Lee, H.-C., Kabat, J.A., and Shibata, E.F. Modulation of Rat Cardiac Sodium Channel by the Stimulatory G-Protein -Subunit. J. Physiol. (Lond.) 518.2:371-384, 1999.

2. Yarbrough T., Lu, T., Lee, H.-C., and Shibata, E.F. Localization of Cardiac Sodium Channels in Caveolin-Rich Membrane Domains: Regulation of Sodium Current Amplitude. Circ. Res. 90:443-449, 2002.

3. Shibata E.F., Brown TLY, Washburn ZW, Bai J, Revak TJ, Butters CA. Autonomic Regulation of Voltage-Gated Cardiac Ion Channels. Journal of Cardiovascular Electrophysiology, 17(5):S34-S42, 2006.