Date Thesis Awarded

5-2011

Document Type

Honors Thesis

Degree Name

Bachelors of Arts (BA)

Department

Biology

Advisor

Margaret Somosi Saha

Committee Member

Mark H. Forsyth

Committee Member

Diane C. Shakes

Committee Member

Gregory D. Smith

Abstract

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.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Comments

Thesis is part of Honors ETD pilot project, 2008-2013. Migrated from Dspace in 2016.

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