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Brennan, J. A.

Publications and source records attributed to Brennan, J. A..

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Flexible and transparent silver nanowire structures for multifunctional electrical and optical biointerfacing

Transparent microelectrodes have recently emerged as a promising approach to combine electrophysiology with optophysiology for multifunctional biointerfacing. High-performance flexible platforms that allow seamless integration with soft tissue systems for such applications are urgently needed. Here, silver nanowires (Ag NWs)-based transparent microelectrodes and interconnects are designed to meet this demand. The Ag NWs percolating networks are patterned on flexible polymer substrates using an innovative photolithography-based solution-processing technique. The resulting nanowire networks exhibit a high average optical transparency of 76.1-90.0% over the visible spectrum, low normalized electrochemical impedance of 3.4-15 {Omega} cm2 at 1 kHz which is even better than those of opaque solid Ag films, superior sheet resistance of 11-25 {Omega} sq-1, excellent mechanical stability up to 10,000 bending cycles, good biocompatibility and chemical stability. Studies on Langendorff-perfused mouse and rat hearts demonstrate that the Ag NWs microelectrodes enable high-fidelity real-time monitoring of heart rhythm during co-localized optogenetic pacing and optical mapping with negligible light-induced electrical artifacts. This proof-of-concept work illustrates that the solution-processed, transparent, and flexible Ag NWs networks are a promising candidate for the next-generation of large-area multifunctional biointerfaces for interrogating complex biological systems in basic and translational research.

bioengineering

Evidence of Superior and Inferior Sinoatrial Nodes in the Mammalian Heart

The initiation of rhythmic heartbeat is the earliest manifestation of new life after conception. A normal heartbeat originates as an action potential in a group of pacemaker cells of the sinoatrial node (SAN)1. Pacemaker cells are evident since early embryogenesis when the entire sinus venosus exhibits electric automaticity and possesses specific gene expression profile distinct from that of working myocardium2,3. During the subsequent looping and ballooning stages of cardiac development, pacemaker cells eventually localize into SAN near the superior vena cava (SVC) when the two horns of the sinus venosus coil in formation of the atria2. The heart rate and anatomical site of origin of pacemaker activity dynamically change in response to various physiological input such as autonomic stimuli and pharmacological interventions4. However, the mechanisms of dominant pacemaker shift are not well understood. Here, we present functional and molecular evidence of two competing right atrial pacemakers localized near the SVC and the inferior vena cava (IVC), which we call the superior and inferior SANs: sSAN and iSAN. Using ex vivo optical mapping techniques and RNA sequencing of rat and human hearts, we demonstrate that sSAN and iSAN preferentially control the fast and slow heart rates during sympathetic or parasympathetic stimulation, respectively. RNAseq confirmed unique transcriptional profiles of sSAN and iSAN, which differs from both atria and ventricles. We speculate that the anatomical locations of sSAN and iSAN are a result of the way the two horns of the sinus venosus twist into a mature chambered heart. We anticipate these findings would clarify previously observed migration of dominant pacemaker and corresponding changes in P-wave morphology in many species. Furthermore, we expect these findings will shed light onto pathogenesis of aberrant pacemakers responsible for life-threatening arrhythmias near orifices of other major vessels: SVC and IVC, coronary sinus, pulmonary veins, aorta and the right ventricular outflow tract.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology