# The beta1-adrenergic receptor in the heart

## TL;DR

This paper reviews the role of the beta1-adrenergic receptor in heart function and disease, highlighting its signaling pathways and therapeutic potential.

## Contribution

A comprehensive review of β1-AR's structure, signaling, and role in cardiac diseases with implications for targeted therapies.

## Key findings

- β1-AR activation has both beneficial and harmful effects on the heart depending on its intensity and duration.
- β1-AR signaling involves multiple pathways, including G protein-dependent and -independent routes.
- Abnormal β1-AR activity is linked to heart diseases, making it a key target for drug development.

## Abstract

beta1-adrenergic receptor (β1-AR) belongs to G protein-coupled receptors, regulating cardiac physiological and pathological process through complex signaling pathways. Physiologically, the activation of β1-AR produces positive chronotropic, positive inotropic and positive dromotropic effects in the heart. However, excessive or sustained activation of β1-AR can cause myocardial injury, arrhythmias, and heart failure. The β1-AR in the heart exhibits tissue-specific distribution patterns and subcellular localization features adapted to its function within cardiomyocytes. Upon ligand binding, the β1-AR undergoes conformational changes and transmits signaling through G protein-dependent pathways (β1-AR/Gs and β1-AR/Gi) as well as a G protein-independent pathway (β1-AR/β-arrestin) to regulate cardiac activity. Subsequently, the β1-AR can either dissociate from G protein to undergo desensitization and terminate signal transduction, or it can be endocytosed into the cell, transported to the lysosome to be degraded, or returned to the plasma membrane to continue its function. Additionally, it has been found that β1-AR can cause or exacerbate heart disease when abnormal changes occur in its distribution density, localization, and mediated downstream signaling pathways. Therefore, β1-AR represents an important pharmacotherapeutic target for the treatment of cardiac diseases. Among the relevant therapeutic agents, β1-AR blockers designed specifically against β1-AR have evolved to the third generation. This review comprehensively analyzes β1-AR from perspectives including its research history, expression, and distribution in the heart, protein structure, signaling pathways, and associations with cardiac diseases.