Background: Autonomic neurons are clustered in ganglionated plexi (GP) epicardially where they play a key role in controlling heart rhythm and triggering arrhythmias. However, little is known about the functional properties of GP neurons, especially in humans where no cellular electrophysiological recordings have been performed.
Objective: To perform pioneering whole cell recordings and imaging of human GP neurons to reveal their functional and structural properties.
Methods: Adipose tissue samples containing right atrial GP were obtained during valve or bypass surgeries (mean patient age: 65.25 ± 4.03 y, mean BMI: 23.73 ± 0.17). GP neurons were studied via whole cell patch clamp electrophysiology, and dye-filled for morphological characterization.
Results: Human GP neurons, encased by S100B+ glia (1A), showed long and complex dendritic morphology [length: 244 ± 86 μm (1B, C, D); branches: 3.40 ± 3.32/neuron, n=5]. Many primary dendrites extended from GP soma (9 ± 1.6) forming a somatic “halo” (1B, D). GP neurons fired action potentials with current injection (0.4 - 1 nA, n=6): we observed both accommodating (4/6; 1E) and non-accommodating patterns (2/6; 1F), as well as voltage-gated channel currents (1G). Synaptic currents occurred spontaneously, and could be evoked by nerve stimulation in a subset of neurons (1H, I).
Conclusion: We have successfully developed whole cell recording techniques from human GP neurons, revealing significantly increased functional and morphological complexity compared with animal models. This characterization will enable the detection of changes in human GP neuron excitability and synaptic activity that could drive cardiac arrhythmias.$$graphic_{341D414C-C34F-45EB-8F7D-E74C00B1E5CF}$$