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NITRIC OXIDE ENHANCES TRANSMITTER RELEASE AT THE MAMMALIAN NEUROMUSCULAR JUNCTION VIA A CGMP-MEDIATED MECHANISM

by Nickels, Travis John

Abstract (Summary)
Nitric Oxide (NO) has been the subject of a tremendous amount of research over the past two decades; however, its precise mechanism of action at the mammalian neuromuscular junction (NMJ) remains poorly understood. We tested the hypothesis that NO functions endogenously via a cGMP-dependent mechanism to enhance transmitter release when intracellular adenosine levels are low. Quantal release was evaluated using the rat phrenic-nerve/hemidiaphragm preparation via intracellular recording techniques. A variety of drugs were used to elucidate NO’s primary mechanism. Application of Sodium Nitrite and L-Arginine (NO donors) alone was unable to significantly alter transmitter release. However, when adenosine receptors were blocked with DPCPX, a selective adenosine A1-receptor antagonist, application of these NO-donors resulted in a significant enhancement of transmitter release relative to control. The elevation of cGMP with YC-1, a guanylyl cyclase activator, also yielded a significant enhancement. However, in the presence of ODQ, a selective guanylyl cyclase inhibitor, the previously established excitatory effect of Sodium Nitrite and L-Arginine was abolished. These results suggest that NO functions to enhance neurotransmission at the mammalian NMJ via a cGMP-mediated mechanism. Since this excitatory effect was only observed when adenosine receptors were blocked, it is likely that NO and adenosine are acting on the same calcium channel. Previously, it has been shown that adenosine inhibits N-type calcium channels; therefore, the present study suggests that NO functions to enhance N-type calcium channel activity. Since adenosine levels should be low under in vivo conditions, we believe that NO normally functions to enhance transmitter release; however, this action can be blocked when adenosine levels increase.
Bibliographical Information:

Advisor:

School:Miami University

School Location:USA - Ohio

Source Type:Master's Thesis

Keywords:nitric oxide neuromuscular junction quantal release neurotransmission adenosine n type calcium channels

ISBN:

Date of Publication:01/01/2006

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