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AREA OF EXPERTISE and PRIMARY INTEREST
My long term goal is to understand how electrical activity in intracardiac neurons affects heart function. Intracardiac neurons are components of the autonomic nervous system and are important in regulating heart activity. In humans, these neurons are grouped to form the intracardiac ganglia, located mainly on the epicardial surface of the atria and surrounded by adipose tissue referred to as "fat pads". It has long been recognized that the cardiovascular system can function independently of neural and hormonal control. However, optimization of heart rate function in response to exercise, temperature stress and high blood pressure, among others; depends on coordination of the nervous system within the heart with the central (brain) and autonomic nervous systems. Intracardiac ganglia are often referred to as the "little brain of the heart" because they are comprised of a complex and intricate network of nerves comprising the parasympathetic and sympathetic branches of the autonomic nervous system, coupled with sensory neurons and nerves that permit communication among ganglia within the heart. The influence of intracardiac ganglia on heart activity is mainly inhibitory, exerted through parasympathetic neurons. Work in my laboratory has been directed at understanding the electrochemical signaling of principal neurons in mammalian intracardiac ganglia. Electrical changes across the cell membrane are used by excitable cells to communicate within each other and with their target cells. These changes can be caused from electrical or chemical signaling and can give rise to a regenerative change of the membrane voltage, called an action potential (AP). These membrane voltage changes are the result of currents created by charged ions traversing channels formed by proteins spanning the membrane of the cell. Potassium channels are known for their participation in maintaining the cell resting potential, repolarization of the AP and synaptic transmission. My current focus is on the electrophysiological properties of large conductance calcium-activated potassium channels and their role on the AP activity of intracardiac neurons. Recent immunohistochemical studies in my laboratory have shown that the a subunit of the BK channel is widely expressed in intracardiac neurons (Figure 1). In addition, electrophysiological and pharmacological studies on isolated intracardiac neurons have shown large calcium dependent potassium current. Figure 1. Positive staining of intracardiac neurons with an antibody that recognizes the a subunit of the BK channel.  An unexpected and novel finding from my laboratory that arose from our work on ionic currents was evidence for the presence of a "cardiac type" sodium channel in intracardiac neurons. This type of sodium channel has been widely studied in cardiac muscle and is responsible for the depolarizing phase of the cardiac AP. It is known that mutations on the gene that encodes this channel are related to several life threatening arrhythmogenic diseases. This finding suggests that a mutation in this gene (SCN5A) may not only create the substrate for the development of ventricular arrhythmias, but may also influence neural control of the heart, thus providing the trigger that precipitates the arrhythmia. Major PublicationsFunctional expression of "cardiac-type" Nav1.5 sodium channel in canine intracardiac ganglia. Spontaneous miniature hyperpolarizations affect threshold for action potential generation in mudpuppy cardiac neurons.
Single channels underlying miniature outward currents (SMOCs) in mudpuppy cardiac neurons. Ca2(+)-induced Ca2(+) release activates spontaneous miniature outward currents in parasympathetic cardiac neurons.
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Medical Research Saves Lives Cardiac Arrhythmias - Cardiovascular Diseases - Sudden Cardiac Arrest  |
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