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Electrophysiological properties of colon‐projecting sensory neurons in male and female serotonin transporter knockout (SERT KO) rats

Irritable bowel syndrome (IBS) is a gut motility disorder and pain disorder associated with altered serotonin signaling, particularly in women. We used whole cell recordings of spinal sensory neurons in vitro from SERT KO and wild‐type (WT) rats to determine if sex‐related alterations in neuron excitability could contribute to gut pain. Neurons studied were <30–45 microns in diameter. There were no differences in resting membrane potential or input resistance of neurons from WT or SERT KO rats of either sex. The rheobase of neurons from female SERT KO rats was higher than neurons from male WT and SERT KO rats. Female SERT KO neurons when depolarized fired more action potentials than neurons from female WT rats. The variance in neuronal firing rate in female SERT KO neurons was greater than female WT neurons. Action potential firing was not different in neurons from male SERT KO and WT rats. There was no difference in the proportion of neurons with TTX sensitive and resistant action potentials in WT and SERT KO rats of either sex. Colon projecting sensory neurons SERT KO female rats exhibited elevated action potential firing without a change in membrane potential or input resistance. Increased responsiveness of colon‐projecting sensory neurons to membrane depolarization may contribute to visceral hypersensitivity in female IBS patients. (Support: R21NS075841)