The long QT syndrome genes HERG1 and KCNQ1, encoding K+ channels critical to repolarization rate and repolarization reserve in cardiac cells thereby the likelihood of arrhythmias, are both comprised of two isoforms: HERG1a and HERG1b, and KCNQ1a and KCNQ1b, respectively. Expression of these genes is dynamic depending on differentiation status and disease states. We identified their core promoter regions and transcription start sites. Our data suggest that HERG1a and HERG1b, and KCNQ1a and KCNQ1b represent independent transcripts, instead of being alternatively spliced variants of the same gene, for they each have their own transcription start sites and their own promoter regions. We obtained the data pointing to the potential role of Sp1 in transactivating these genes. We compared expression profiling of these genes across a variety of human tissues. Consistent with the general lack of cis-elements for cardiac-specific transcription factors and the presence of multiple sites for ubiquitous Sp1 sites in the core promoter regions of HERG1a/HERG1b and KCNQ1a/KCNQ1b genes, the transcripts demonstrated widespread distribution across a variety of human tissues. We further revealed that the mRNA levels of all HERG1 and KCNQ1 isoforms are asymmetrically distributed within the heart, being more abundant in the right relative to the left atria and ventricles. The finding provides an explanation for the known interventricular gradients of I_Ks and I_Kr and of cardiac repolarization as well. Our study may help us understand the molecular mechanisms for arrhythmogenesis since heterogeneity of ion channel activities is an important substrate for arrhythmia to occur.