Signaling Modulation in Cells that Control Gastrointestinal Motility
Loera Valencia, Raúl
Life is sustained in part by the motor activity of the gastrointestinal tract. The motility patterns in the gastrointestinal tract are orchestrated by the interplay of neurogenic and myogenic governing mechanisms. The myenteric neurons modulate the peristaltic reflex through circuits of sensory, motor and interneurons, while interstitial cells of Cajal (ICC) pace the generation of rhythmic voltage oscillations in the smooth muscle known as slow waves. Both systems act together to generate diverse motility patterns in the gut. Myenteric neurons and interstitial cells of Cajal modulate their activity through signaling of neurotransmitters and its effect on the gating of ionic channels. In this work we use diverse molecular techniques to address particular problems in the signalling of myenteric neurons and interstitial cells of Cajal. Myenteric neurons use ATP as excitatory neurotransmitter through P2X receptor signalling, however the presence of P2X3 does not play a role in the normal physiology of guinea pig small intestinal motility. We propose this subunit has a function in postnatal development. Our results show reduction of P2X3 positive myenteric neurons during postnatal development and increase of P2X5 positive neurons to adulthood, whilst appearance of P2X2 and P2X4 remained unchanged. This regulation does not alter ATP sensibility in cultured neurons from neonatal or adult guinea pigs. Murine colonic ICC could participate in the modulation of colon motility through muscarinic cholinergic signalling; we provide experimental evidence showing that muscarinic stimulation of ICC blocked K+ channel activity in primary cultures. The application of a Kv7 blocker also abolished this activity and activated a maxi channel in ICC. Single cell RT-PCR and double immunostaining of colons revealed Kv7.5 positive ICC-IM and its dense cholinergic innervation. We suggest expanding the use of molecular techniques to approach basic physiological problems in gut motility.
Fecha de publicación2014-02
Tipo de publicacióndoctoralThesis
Área de conocimientoBIOLOGÍA MOLECULAR
DirectorBarajas López, Carlos
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