Augustus O. Grant, MD, PhD

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Services

• Heart Rhythm Services

Department / Division:
Medicine / Cardiovascular Medicine

Address:
DUMC 3504
Durham, NC 27710

Appointment Telephone:
919-684-3901

Office Telephone:
919-684-3901

Fax Telephone:
919-681-8978

• MB ChB, University of Edinburgh (Scotland), 1971

• University of California, San Francisco, 1972-1975
• University of Manitoba (Canada), 1975-1977
• Duke University Medical Center, 1977-1980

Clinical Interests:
Cardiac arrhythmias

Research Interests:

This laboratory seeks to understand the molecular events that control excitation in cardiac muscle and the mechanisms by which excitation  is modified by drugs.  The experimental models include the isolated cardiac myocyte, the frog oocyte and mammalian cells expressing mRNA transcripts of wild-type and mutant channels.  The experimental techniques include DNA and RNA manipulation, whole cell voltage clamping and the extracellular patch clamping.  The current focus of the laboratory is the voltage gated sodium channel.  The problems under study include:

1) The functional effects of the derangements occurring during
myocardial ischemia on channel function.
2) The mechanisms of blockade of channels by antiarrhythmic drugs.
3) The relationship between channel structure and antiarrhythmic drug
binding.
4) The development of models to describe the interaction of anti-
arrhythmic drugs with membrane channels.

These studies should provide a clearer understanding of the cellular basis of cardiac arrhythmias and the mechanisms by which they are terminated by drug.

Representative Publications:
Starmer CF, Romashko DN, Reddy RS, Zilberter Y, Starobin J, Grant AO, Krinsky VI: A Proarrhythmic Response to Potassium Channel Blockade: Numerical Studies of Torsade de Pointes. Circulation 92:595-605, 1995. (1995)

Zilberter YI, Starmer CF, Grant AO: Late Na Channels in Cardiac Cells: The Physiological Role of Background Na Channels Biophysical J 67:153-160, 1994. (1994)

Whalley DW, Wendt DJ, Starmer CF, Rudy Y, Grant AO: Voltage-Independent Effects of Extracellular K+ on the Na+ Current and Phase O of the Action Potential in Isolated Cardiac Myocytes. Circ Tes 75:491-502, 1994. (1994)

Grant AO, Wendt DJ, Zilberter Y, Starmer CF: Kinetics of Interaction of Disopyramide with the Cardiac Sodium Channel: Fast Dissociation from Open Channels at Normal Rest Potentials. J Membr Biol 136:199-214, 1993. (1993)

Wendt DJ, Starmer CF, Grant AO: Kinetics of interaction of the lidocaine metabolite, glycylxylidide with the cardiac sodium channel: Additive blockade with lidocaine. Cir Res 70:1254, 1992. (1992)

Barber MJ, Wendt DJ, Starmer CF, Grant AO: Blockade of cardiac sodium channels: competition between the permeant ion and antiarrhythmic drugs. J Clin Invest 90:368-381, 1992. (1992)