| Abstract No.: | C-E3173 |
| Country: | Canada |
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| Title: | PK2 INDUCES LONG-LASTING CHANGES IN THE EXCITABILITY OF AREA POSTREMA NEURONS |
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| Authors/Affiliations: | 1 Mathew V. Ingves*; 1 Alastair V. Ferguson;
1 Queens University, Department of Physiology, Kingston, ON, Canada
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| Content: | Objectives
Prokineticin 2 (PK2) is a novel peptide shown to be expressed in the GI tract and in the central nervous system. PK2 mRNA is expressed rhythmically in the suprachiasmatic nucleus, which identifies this peptide as a key output molecule involved in circadian signaling and control of sleep-wake cycles, feeding, metabolism, and neuroendocrine function.
The area postrema (AP) is a hindbrain structure critical for integrating and relaying homeostatic signals to hypothalamic and medullary autonomic control centres. The AP lacks the normal blood brain barrier, and thus can monitor peripheral and blood-borne signals. AP neurons express a high density of PK2 receptors, suggesting that this structure is an ideal site where PK2 acts as an autonomic regulator in the central nervous system.
Materials and Methods
We used whole cell current-clamp recordings to investigate the effects of rapid application of PK2 on the excitability of dissociated AP neurons.
Results
The responsiveness of a total of 21 dissociated AP neurons to local application of PK2 (1 µM; 5-10 s) revealed that 62% of AP neurons were sensitive to PK2. AP neurons tested had a mean baseline membrane potential of -48.3 ± 7.6 mV, and membrane hyperpolarization was observed in 10 out of 21 neurons (mean, -12.1 ± 6.4 mV). A smaller proportion of AP neurons responded to PK2 application with depolarizations (n = 3; mean, 17.1 ± 10.0 mV). The resulting effects were reversible and long-lasting with a mean duration of 452.8 ± 189.4 s.
Conclusions
These data show that brief application of PK2 has the ability to induce long-lasting changes in AP neuronal activity. Furthermore, PK2 acts on different subpopulations of AP neurons to produce both excitatory and inhibitory actions on membrane potential. These observations suggest potentially important mechanisms through which PK2 regulates circadian autonomic function.
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