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The sinoatrial node (SAN) maintains a rhythmic heartbeat; therefore, a better understanding of factors that drive SAN development and function is crucial to generation of potential therapies, such as biological pacemakers, for sinus arrhythmias. Here, we determined that the LIM homeodomain transcription factor ISL1 plays a key role in survival, proliferation, and function of pacemaker cells throughout development. Analysis of several Isl1 mutant mouse lines, including animals harboring an SAN-specific Isl1 deletion, revealed that ISL1 within SAN is a requirement for early embryonic viability. RNA-sequencing (RNA-seq) analyses of FACS-purified cells from ISL1-deficient SANs revealed that a number of genes critical for SAN function, including those encoding transcription factors and ion channels, were downstream of ISL1. Chromatin immunoprecipitation assays performed with anti-ISL1 antibodies and chromatin extracts from FACS-purified SAN cells demonstrated that ISL1 directly binds genomic regions within several genes required for normal pacemaker function, including subunits of the L-type calcium channel, Ank2, and Tbx3. Other genes implicated in abnormal heart rhythm in humans were also direct ISL1 targets. Together, our results demonstrate that ISL1 regulates approximately one-third of SAN- specific genes, indicate that a combination of ISL1 and other SAN transcription factors could be utilized to generate pacemaker cells, and suggest ISL1 mutations may underlie sick sinus syndrome., Introduction Rhythmic contraction of the heart is controlled by electrical impulses generated by pacemaker cells of the sinoatrial node (SAN). Abnormalities in SAN development lead to cardiac arrhythmia and sudden [...]

ABSTRACT The present study was designed to investigate the protective effects of 4-guanidino-n-butyl syringate (leonurine), a compound in Herba Leonuri (HL) on ischemic rat heart to determine the protective mechanisms [...]

Abstract This work aims to describe some electrophysiological changes promoted by the aqueous extract (AEx) from Averrhoa carambola leaves in guinea pig heart. The experiments were carried out on isolated [...]

I. Introduction II. Action Potential Generation by the Single Cardiac Cell III. Fundamental Biophysical Principles of Propagation A. Continuous propagation B. Principles of discontinuous propagation C. The safety of propagation [...]

I. GENERAL COMMENTS In this review, we provide a brief historical background regarding gap junction structure and physiology and then concentrate on reviewing several areas of active research in the [...]

Theory without fact is fantasy, but fact without theory is chaos. C. O. Whitman (334) I. INTRODUCTION A. Scope In birds and mammals, the four chambers of the formed heart [...]

Owens, Gary K. Regulation of Differentiation of Vascular Smooth Muscle Cells. Physiol. Rev. 75: 487-517, 1995. -- The vascular smooth muscle cell (SMC) in mature animals is a highly specialized [...]

THE PAPILIO BUTTERFLY HAS LIGHT SENSITIVITY IN THE GENITALIA, WHICH APPEARS TO BE CRUCIAL FOR REPRODUCTIVE BEHAVIOR Butterflies sense light with their genitalia. Four photoreceptor cells in the genitalia mediate [...]