The goal of this laboratory is understanding the molecular events that control excitation in cardiac muscle and the mechanisms by which excitation is modified by drugs.
Experimental models include:
- The isolated cardiac myocyte
- The frog oocyte
- Mammalian cells expressing mRNA transcripts of wild-type and mutant channels
- Embryonic stem cells that express mutant ion channels
Experimental techniques include:
- DNA and RNA manipulation
- Whole cell voltage clamping
- Extracellular patch clamping
A current focus of the laboratory is the voltage gated sodium channel. The problems under study include:
- The mechanisms of blockade of channels by antiarrhythmic drugs and neurotransmitters
- The relationship between channel structure and antiarrhythmic drug binding
- The development of models to describe the interaction of antiarrhythmic drugs with membrane channels
- Influence of Na-channel mutations on channel gating. These studies include mutations associated with the long QT syndrome (LQTS)
- The development of in vitro and in vivo models of LQTS and Brugada syndrome
These studies should provide a clearer understanding of the cellular basis of cardiac arrhythmias and the mechanisms by which they are terminated by drugs.
- Chandra R, Starmer CF, Grant, AO. Multiple effects of KPQ deletion mutation on gating of human cardiac Na+ channels expressed in mammalian cells. Am J Physiol 274:H643, 1998.
- Chandra R, Chauhan VS, Starmer CF, Grant AO. ß-adrenergic action on wild-type and KPQ mutant human cardiac Na+ channels: shift in gating but no change in Ca2+/Na+ selectivity. Cardiovasc Res 42:490, 1999.
- Chauhan VS, Tuvia S, Buhusi M, Bennett V, Grant AO. Abnormal cardiac Na channel properties and QT-heart rate adaptation in neonatal ankyrinB knockout mice. Circ Res 86:441, 2000.
- Grant AO, Chandra R, Keller C, Carboni M, Starmer CF. Block of wild-type and inactivation-deficient cardiac sodium channels IFM/QQQ stably expressed in mammalian cells. Biophysical J 79:3019, 2000.
- Grant AO, Carboni M, Neplioueva V, Starmer CF, Memmi M, Napolitano C, Priori S. Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation. J Clin Invest 110: 1201, 2002.
Augustus O. Grant, MD, Director
Zhu-Shan Zhang, MD, PhD
Office: 2301 Erwin Road 7th Floor, Room #7407, Durham, NC, 27710
Campus mail: DUMC Box 3504, Durham, NC, 27710