In the last decade, I was involved with analytical tools to define the molecules involved in smooth muscle excitability. In particular, my laboratory cloned the large-conductance Ca2+-dependent K+ channel (MaxiK) and associated regulatory beta-subunits that are key elements in the regulation of smooth muscle tone and brain excitability. The next challenge in modern Physiology is to integrate how single molecules with molecular partners form functional networks and how their dynamic changes in subcellular localization/associations result in their particular physiological functions. Our laboratory main focus is to elucidate K+ channel-signaling networks in the vascular and cardiac systems in health and disease. One emerging concept is that ion channels not only have conductive functions but are also signaling molecules. We are particularly interested in the remodeling of K+ channel-signaling networks by circulating and local hormones (estrogen, thromboxane A2, angiotensin II), and by pathophysiological stimuli like stress. These studies are performed in native vascular smooth muscle (e.g. human coronaries), in cardiac myocytes and mitochondria, and in expression systems. We apply modern technologies including molecular genetics, physiological proteomics, and novel nanomicroscopies and optical methods to map at the subcellular level signaling complexes and follow their dynamics. Key elements in our investigations are the recognition of genomic, molecular and cell biological mechanisms and the visualization of protein interactions/remodeling in individual cells.