QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 22, 2008, 28(43):10905-10917; doi:10.1523/JNEUROSCI.2237-08.2008

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Khaliq, Z. M. Articles by Bean, B. P. Search for Related Content PubMed PubMed Citation Articles by Khaliq, Z. M. Articles by Bean, B. P.

 Previous Article  |  Next Article 

Cellular/Molecular
Dynamic, Nonlinear Feedback Regulation of Slow Pacemaking by A-Type Potassium Current in Ventral Tegmental Area Neurons

Zayd M. Khaliq and Bruce P. Bean

Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115

Correspondence should be addressed to Zayd M. Khaliq, Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115. Email: zayd_khaliq{at}hms.harvard.edu

We analyzed ionic currents that regulate pacemaking in dopaminergic neurons of the mouse ventral tegmental area by comparing voltage trajectories during spontaneous firing with ramp-evoked currents in voltage clamp. Most recordings were made in brain slice, with key experiments repeated using acutely dissociated neurons, which gave identical results. During spontaneous firing, net ionic current flowing between spikes was calculated from the time derivative of voltage multiplied by cell capacitance, signal-averaged over many firing cycles to enhance resolution. Net inward interspike current had a distinctive nonmonotonic shape, reaching a minimum (generally <1 pA) between –60 and –55 mV. Under voltage clamp, ramps over subthreshold voltages elicited a time- and voltage-dependent outward current that peaked near –55 mV. This current was undetectable with 5 mV/s ramps and increased steeply with depolarization rate over the range (10–50 mV/s) typical of natural pacemaking. Ramp-evoked subthreshold current was resistant to -dendrotoxin, paxilline, apamin, and tetraethylammonium but sensitive to 4-aminopyridine and 0.5 mM Ba²⁺, consistent with A-type potassium current (I_A). Same-cell comparison of currents elicited by various ramp speeds with natural spontaneous depolarization showed how the steep dependence of I_A on depolarization rate results in small net inward currents during pacemaking. These results reveal a mechanism in which subthreshold I_A is near zero at steady state, but is engaged at depolarization rates >10 mV/s to act as a powerful, supralinear feedback element. This feedback mechanism explains how net ionic current can be constrained to <1–2 pA but reliably inward, thus enabling slow, regular firing.

Key words: I_A; I_K; 4-aminopyridine; spontaneous firing; A-type; dopaminergic neurons; VTA

---

Received May 17, 2008; revised Sept. 10, 2008; accepted Sept. 11, 2008.

Correspondence should be addressed to Zayd M. Khaliq, Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115. Email: zayd_khaliq{at}hms.harvard.edu

This article has been cited by other articles:

				C. A. Deister, C. S. Chan, D. J. Surmeier, and C. J. Wilson Calcium-Activated SK Channels Influence Voltage-Gated Ion Channels to Determine the Precision of Firing in Globus Pallidus Neurons J. Neurosci., July 1, 2009; 29(26): 8452 - 8461. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help