Physiologic regulation of heart rate and blood pressure involves connexin 36–containing gap junctions

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Abstract
Chronically elevated sympathetic nervous activity underlies many cardiovascular diseases. Elucidating the mechanisms contributing to sympathetic nervous system output may reveal new avenues of treatment. The contribution of the gap junctional protein connexin 36 (Cx36) to the regulation of sympathetic activity and thus blood pressure and heart rate was determined using a mouse with specific genetic deletion of Cx36. Ablation of the Cx36 protein was confirmed in sympathetic preganglionic neurons of Cx36‐knockout (KO) mice. Telemetric analysis from conscious Cx36 KO mice revealed higher variance in heart rate and blood pressure during rest and activity compared to wild‐type (WT) mice, and smaller responses to chemoreceptor activation when anesthetized. In the working heart–brain stem preparation of the Cx36‐KO mouse, respiratory‐coupled sympathetic nerve discharge was attenuated and responses to chemoreceptor stimulation and noxious stimulation were blunted compared to WT mice. Using whole cell patch recordings, sympathetic preganglionic neurons in spinal cord slices of Cx36‐KO mice displayed lower levels of spikelet activity compared to WT mice, indicating reduced gap junction coupling between neurons. Cx36 deletion therefore disrupts normal regulation of sympathetic outflow with effects on cardiovascular parameters.—Lall, V.K., Bruce, G., Voytenko, L., Drinkhill, M., Wellershaus, K., Willecke, K., Deuchars, J., Deuchars, S. A. Physiologic regulation of heart rate and blood pressure involves connexin 36–containing gap junctions. FASEB J. 31, 3966–3977 (2017). www.fasebj.org —Lall, Varinder K., Bruce, Gareth, Voytenko, Larysa, Drinkhill, Mark, Wellershaus, Kerstin, Willecke, Klaus, Deuchars, Jim, Deuchars, Susan A. Physiologie regulation of heart rate and blood pressure involves connexin 36–containing gap junctions. FASEB J. 31, 3966–3977 (2017)
Funding Information
  • British Heart Foundation (PG/08/120/26338)
  • Biotechnology and Biological Sciences Research Council (BB/1)
  • Wellcome Trust (WT093072MA)

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