Augustus Oliver Grant

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.