Date Thesis Awarded
Honors Thesis -- Access Restricted On-Campus Only
Bachelors of Arts (BA)
Margaret Somosi Saha
Mark H. Forsyth
Diane C. Shakes
Gregory D. Smith
In mammals, the breathing behavior originates in brainstem networks. Neurons of the mammalian respiratory rhythmogenerator, the PreBotzinger complex (preBotC), augment periodic synaptic input to generate robust envelopes of depolarization called inspiratory drive potentials, Calcium-activated non-specific cationic current (I-CAN) has been implicated in drive potential generation via an inositol 1,4,5-trisphosphate (IP3) dependent mechanism. The protein or proteins underlying this current, however, remain unknown. Because of their unique biophysical properties, two homologs of the transient receptor potential (TRP) channel family, TRPM4/5, make attractive candidates for I-CAN. Earlier RT-PCR experiments demonstrated expression of TRPM4/5 mRNAs within the preBotC. Additionally, using anatomical landmarks, earlier immunohistochemistry data demonstrate expression of TRPM4/5 protein in neurons of the inspiratory network. Here, we provide the first functional evidence for TRPM4/5 in the preBotC. Pharmacological inhibition of TRPM4 by a selective inhibitor, 9-phenanthrol, progressively attenuated drive potentials, consistent with a functional role for TRPM4 in inspiratory burst generation. Additionally, we propose a protocol that will facilitate single-channel recordings from preBotC neurons. We conclude that, while not definitive, many lines of evidence now suggest TRPM4/5 channels as the molecular identity of I-CAN.
Goodreau, Adam Mitchell, "TRPM4/5's Role in Inspiratory Calcium-Activated Nonspecific Cation Current" (2011). Undergraduate Honors Theses. William & Mary. Paper 426.
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