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PACAP\/PAC<jats:sub>1<\/jats:sub>receptor signaling increases excitability of neurons within the guinea pig cardiac ganglia, making them a unique system to establish mechanisms underlying PACAP modulation of neuronal function. Calcium influx is required for the PACAP-increased cardiac neuron excitability, although the pathway is unknown. This study tested whether PACAP enhancement of calcium influx through either T-type or R-type channels contributed to the modulation of excitability. Real-time quantitative polymerase chain reaction analyses indicated transcripts for Ca<jats:sub>v<\/jats:sub>3.1, Ca<jats:sub>v<\/jats:sub>3.2, and Ca<jats:sub>v<\/jats:sub>3.3 T-type isoforms and R-type Ca<jats:sub>v<\/jats:sub>2.3 in cardiac neurons. These neurons often exhibit a hyperpolarization-induced rebound depolarization that remains when cesium is present to block hyperpolarization-activated nonselective cationic currents ( I<jats:sub>h<\/jats:sub>). The T-type calcium channel inhibitors, nickel (Ni<jats:sup>2+<\/jats:sup>) or mibefradil, suppressed the rebound depolarization, and treatment with both drugs hyperpolarized cardiac neurons by 2\u20134 mV. Together, these results are consistent with the presence of functional T-type channels, potentially along with R-type channels, in these cardiac neurons. Fifty micromolar Ni<jats:sup>2+<\/jats:sup>, a concentration that suppresses currents in both T-type and R-type channels, blunted the PACAP-initiated increase in excitability. Ni<jats:sup>2+<\/jats:sup>also blunted PACAP enhancement of the hyperpolarization-induced rebound depolarization and reversed the PACAP-mediated increase in excitability, after being initiated, in a subset of cells. Lastly, low voltage-activated currents, measured under perforated patch whole cell recording conditions and potentially flowing through T-type or R-type channels, were enhanced by PACAP. Together, our results suggest that a PACAP-enhanced, Ni<jats:sup>2+<\/jats:sup>-sensitive current contributes to PACAP-induced modulation of neuronal excitability.<\/jats:p>","DOI":"10.1152\/ajpcell.00403.2014","type":"journal-article","created":{"date-parts":[[2015,3,26]],"date-time":"2015-03-26T10:26:43Z","timestamp":1427365603000},"page":"C857-C866","source":"Crossref","is-referenced-by-count":18,"title":["Nickel suppresses the PACAP-induced increase in guinea pig cardiac neuron excitability"],"prefix":"10.1152","volume":"308","author":[{"given":"John D.","family":"Tompkins","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences, College of Medicine, University of Vermont, Burlington, Vermont"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Merriam","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, College of Medicine, University of Vermont, Burlington, 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