Ion-channel mRNA-expression profiling: Insights into cardiac remodeling and arrhythmic substrates

Membrane ion channels and transporters are key determinants of cardiac electrical function. Their expression is affected by cardiac region, hemodynamic properties, heart-rate changes, neurohormones and cardiac disease. One of the important determinants of ion-channel function is the level of ion-channel subunit mRNA expression, which governs the production of ion-channel proteins that traffic to the cell-membrane to form functional ion-channels. Ion-channel mRNA-expression profiling can be performed with cDNA microarrays or high-throughput reverse transcription/polymerase chain reaction (PCR) methods. Expression profiling has been applied to evaluate the dependence of ion-channel expression on cardiac region, revealing the molecular basis of regionally-controlled electrical properties as well as the molecular determinants of specialized electrical functions like pacemaking activity. Ion-channel remodeling occurs with cardiac diseases like heart failure, congenital repolarization abnormalities, and atrial fibrillation, and expression profiling has provided insights into the mechanisms by which these conditions affect cardiac electrical stability. Expression profiling has also shown how hormonal changes, antiarrhythmic drugs, cardiac development and altered heart rate affect ion-channel expression patterns to modify cardiac electrical function and sometimes to produce cardiac rhythm disturbances. This article reviews the information obtained to date with the application of cardiac ion-channel expression profiling. With increasing availability and efficiency of high-throughput PCR methods for ion-channel subunit mRNA-expression characterization, it is likely that the application of ion-channel expression profiling will increase and that it will provide important new insights into the determinants of cardiac electrical function in both physiological and pathological situations.