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Pretreatment with Nonselective Cationic Channel Inhibitors Blunts the PACAP-Induced Increase in Guinea Pig Cardiac Neuron Excitability

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Abstract

Calcium influx is required for the pituitary adenylyl cyclase activating polypeptide (PACAP)-induced increase in guinea pig cardiac neuron excitability, noted as a change from a phasic to multiple action potential firing pattern. Intracellular recordings indicated that pretreatment with the nonselective cationic channel inhibitors, 2-aminoethoxydiphenylborate (2-APB), 1-[β-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole HCl (SKF 96365), and flufenamic acid (FFA) reduced the 20-nM PACAP-induced excitability increase. Additional experiments tested whether 2-APB, FFA, and SKF 96365 could suppress the increase in excitability by PACAP once it had developed. The increased action potential firing remained following application of 2-APB but was diminished by FFA. SKF 96365 transiently depressed the PACAP-induced excitability increase. A decrease and recovery of action potential amplitude paralleled the excitability shift. Since semiquantitative PCR indicated that cardiac neurons express TRPC subunit transcripts, we hypothesize that PACAP activates calcium-permeable, nonselective cationic channels, which possibly are members of the TRPC family. Our results are consistent with calcium influx being required for the initiation of the PACAP-induced increase in excitability, but suggest that it may not be required to sustain the peptide effect. The present results also demonstrate that nonselective cationic channel inhibitors could have other actions, which might contribute to the inhibition of the PACAP-induced excitability increase.

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Acknowledgments

This work was supported in part by NIH grants P20 RR16435, P30 RR032135, and P30 GM103498 to RLP.

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  1. Department of Anatomy and Neurobiology, College of Medicine, University of Vermont, Burlington, VT 05405, USA

    Laura A. Merriam, Carolyn W. Roman, Caitlin N. Baran, Beatrice M. Girard, Victor May & Rodney L. Parsons

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  1. Laura A. Merriam
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  2. Carolyn W. Roman
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  3. Caitlin N. Baran
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  4. Beatrice M. Girard
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  5. Victor May
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  6. Rodney L. Parsons
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Correspondence to Rodney L. Parsons.

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Merriam, L.A., Roman, C.W., Baran, C.N. et al. Pretreatment with Nonselective Cationic Channel Inhibitors Blunts the PACAP-Induced Increase in Guinea Pig Cardiac Neuron Excitability. J Mol Neurosci 48, 721–729 (2012). https://doi.org/10.1007/s12031-012-9763-z

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  • DOI: https://doi.org/10.1007/s12031-012-9763-z

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