Highly regulated motor reflexes observed in gastrointestinal (GI) motility promote nutrient digestion and absorption as well as excretion of indigestible material. Motor reflexes are fundamentally regulated by the enteric nervous system (ENS), and can be modulated by 1) smooth muscle tone changes by the activation of large conductance Ca2+-activated K+ (BK) channels and by 2) intrinsic neuron activation by 5-hydroxytryptamine (5-HT, serotonin). Impairments in the modulation of motor reflexes... Show moreHighly regulated motor reflexes observed in gastrointestinal (GI) motility promote nutrient digestion and absorption as well as excretion of indigestible material. Motor reflexes are fundamentally regulated by the enteric nervous system (ENS), and can be modulated by 1) smooth muscle tone changes by the activation of large conductance Ca2+-activated K+ (BK) channels and by 2) intrinsic neuron activation by 5-hydroxytryptamine (5-HT, serotonin). Impairments in the modulation of motor reflexes cause GI motility disorders. Although GI motility disorders are typically not life threatening, the quality of life of affected individuals can be poor. GI motility disorders are common in obesity that affects millions of people in the United States. GI motility dysfunction in obesity may be caused by perturbations in intestinal 5-HT dynamics. 5-HT located in enterochromaffin (EC) cells of the GI mucosa influences GI motility by coordinating the nerve circuits in the ENS. I investigated 1) the role BK channels in normal GI transit in mice and 2) 5-HT signaling in controlling GI transit in male and female mice fed a high fat diet (HFD) to produce diet-induced obesity (DIO). I used complimentary in vivo and in vitro methods to identify sex differences in small intestinal transit and 5-HT dynamics in obese mice. Overall, I found 1) BK channels are necessary for normal propulsive colonic transit and 2) sex and obesity-related alterations in small intestinal transit and 5-HT signaling. These sex differences in DIO must be considered when designing therapeutic approaches targeting intestinal 5-HT to treat impaired motility in obesity. Show less
