Slack and Slick KNa channels are required for the depolarizing afterpotential of acutely isolated, medium diameter rat dorsal root ganglion neurons

Acta Pharmacol Sin 2008 Aug; 29 (8): 899905

Full-length article

Slack and Slick KNa channels are required for the depolarizing afterpotential of acutely isolated, medium diameter rat dorsal root ganglion neurons1

Shang-bang GAO2,3, Ying WU2,3, Cai-xia L2, Zhao-hua GUO2, Chen-hong LI2,4, Jiu-ping DING2,4

2Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University o

f

Science and Technology, Wuhan 430074, China

Key words

Abstract

Slack; Slick; Na+-activated K+ channels; depolarizing afterpotential; dorsal root ganglion

1This work was supported by the National Natural Science Foundation of China (No 30470449 and 30470646), the Nature Science Fou ndation of Hu azhong University o

f

Science and Technology (No 20071986), and the Province Nature Science Foundation o

f

Hubei (No 2003ABA096).

3Both authors contributed equally to this work.

4Correspondence to Jiu-ping DING and Chen-hong LI.

Ph n 86-27-8779-2153.

Fax [phone].

E-mail [email protected] (Jiu-ping DING)

Ph n 86-27-8779-2026.

Fax [phone].

E-mail [email protected] (Chen-hong LI)

Received 2008-04-15 Accepted 2008-06-03

doi 10.1111/j.1745-7254.2008.00842.x

Aim: Na+-activated K+ (KNa) channels set and stabilize resting membrane potential in rat small dorsal root ganglion (DRG) neurons. However, whether KNa channels play the same role in other size DRG neurons is still elusive. The aim of this study is to identify the existence and potential physiological functions of KNa

channels in medium diameter (2535 m) DRG neurons. Methods: Inside-out and whole-cell patch-clamp were used to study the electrophysiological characterizations of native KNa channels. RTPCR was used to identify the existence of Slack and Slick genes. Results: We report that KNa channels are required for depolarizing afterpotential (DAP) in medium sized rat DRG neurons. In inside-out patches,

KNa channels represented 201 pS unitary chord conductance and were activated by cytoplasmic Na+ [the half maximal effective concentration (EC50): 35 mmol/L] in 160 mmol/L symmetrical K+o/K+i solution. Additionally, these KNa channels also represented cytoplasmic Cl-dependent activation. RTPCR confirmed the existence of Slack and Slick genes in DRG neurons. Tetrodotoxin (TTX, 100 nmol/L) completely blocked the DRG inward Na+ currents, and the following outward currents which were thought to be KNa currents. The DAP was increased when extracellular Na+ was replaced by Li+. Conclusion: We conclude that Slack and

Slick KNa channels are required for DAP of medium diameter rat DRG neurons that regulate...