Interaction Between Mitochondria and Sarcoplasmic Reticulum in Airway Smooth Muscle

The Mayo Clinic Cell and Regenerative Physiology Laboratory is exploring the neural control of airway smooth muscle, specifically the pathophysiology of airway increased force response (hyperreactivity) and increased cell proliferation (remodeling) characteristic of asthma.

Dr. Sieck's lab's research focuses on control of cytoplasmic calcium and its coupling to mechanical responses (excitation-contraction coupling). Researchers in the laboratory are characterizing the basic mechanisms underlying the acetylcholine (ACh)-induced elevation of cytoplasmic calcium and studying how these mechanisms are affected by exposure to pro-inflammatory cytokines, as occurs in asthma.

Dr. Sieck's research team is also systematically examining the signaling cascade involved in coupling the transient elevations of cytoplasmic calcium to contractile responses in airway smooth muscle. As in all muscles, hyperreactivity in the airway smooth muscle imposes increased energetic demands (ATP hydrolysis) and mitochondrial stress.

The Cell and Regenerative Physiology Laboratory is examining the role of mitochondrial signaling in relation to airway smooth muscle exposure to pro-inflammatory cytokines, reactive oxidants and endoplasmic reticulum stress. The lab hypothesizes that this mitochondrial signaling represents a complex physiological signaling cascade that underlies asthma, triggering both airway hyperreactivity and remodeling.