This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Musa, H. Articles by Veenstra, R. D. Search for Related Content PubMed PubMed Citation Articles by Musa, H. Articles by Veenstra, R. D.

Voltage-Dependent Blockade of Connexin40 Gap Junctions by Spermine

Department of Pharmacology, SUNY Upstate Medical University, Syracuse, New York 13210

Correspondence: Address reprint requests to Richard D. Veenstra, Ph.D., Dept. of Pharmacology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210. Tel.: 315-464-5145; Fax: 315-464-8014; E-mail: veenstrr{at}upstate.edu.

The effects of spermine and spermidine, endogenous polyamines that block many forms of ion channels, were investigated in homotypic connexin (Cx)-40 gap junctions expressed in N2A cells. Spermine blocked up to 95% of I_j through homotypic Cx40 gap junctions in a concentration- and transjunctional voltage (V_j)-dependent manner. V_j was varied from 5 to 50 mV in 5-mV steps and the dissociation constants (K_m) were determined from spermine concentrations ranging from 10 µM to 2 mM. The K_m values ranged from 4.9 mM to 107 µM for 8.6 V_j 37.7 mV, within the physiological range of intracellular spermine for V_j 20 mV. The K_m values for spermidine were 5 mM. Estimates of the electrical distance () for spermine (z = +4) and spermidine (z = +3) were 0.96 and 0.76 respectively. Cx40 single channel conductance was 129 pS in the presence of 2-mM spermine and channel open probability was significantly reduced in a V_j-dependent manner. Similar concentrations of spermine did not block I_j through homotypic Cx43 gap junctions, indicating that spermine selectively blocks Cx40 gap junctions. This is contrary to our previous findings that large tetraalkylammonium ions, also known to block several forms of ion channels, block junctional currents (I_j) through homotypic connexin Cx40 and Cx43 gap junctions.

This article has been cited by other articles:

				X. Lin and R. D. Veenstra Effect of Transjunctional KCl Gradients on the Spermine Inhibition of Connexin40 Gap Junctions Biophys. J., July 15, 2007; 93(2): 483 - 495. [Abstract] [Full Text] [PDF]

				Y. Zhang, X. Niu, T. I. Brelidze, and K. L. Magleby Ring of Negative Charge in BK Channels Facilitates Block by Intracellular Mg2+ and Polyamines through Electrostatics J. Gen. Physiol., July 31, 2006; 128(2): 185 - 202. [Abstract] [Full Text] [PDF]

				J. Gemel, X. Lin, R. D. Veenstra, and E. C. Beyer N-terminal residues in Cx43 and Cx40 determine physiological properties of gap junction channels, but do not influence heteromeric assembly with each other or with Cx26 J. Cell Sci., June 1, 2006; 119(11): 2258 - 2268. [Abstract] [Full Text] [PDF]

				X. Lin, E. Fenn, and R. D. Veenstra An amino-terminal lysine residue of rat connexin40 that is required for spermine block J. Physiol., January 15, 2006; 570(2): 251 - 269. [Abstract] [Full Text] [PDF]

				X. Hu, M. Ma, and G. Dahl Conductance of Connexin Hemichannels Segregates with the First Transmembrane Segment Biophys. J., January 1, 2006; 90(1): 140 - 150. [Abstract] [Full Text] [PDF]

				M. C. Puljung, V. M. Berthoud, E. C. Beyer, and D. A. Hanck Polyvalent Cations Constitute the Voltage Gating Particle in Human Connexin37 Hemichannels J. Gen. Physiol., October 25, 2004; 124(5): 587 - 603. [Abstract] [Full Text] [PDF]

				H. Musa, E. Fenn, M. Crye, J. Gemel, E. C. Beyer, and R. D. Veenstra Amino terminal glutamate residues confer spermine sensitivity and affect voltage gating and channel conductance of rat connexin40 gap junctions J. Physiol., June 15, 2004; 557(3): 863 - 878. [Abstract] [Full Text] [PDF]

				D. Locke, I. V. Koreen, J. Y. Liu, and A. L. Harris Reversible Pore Block of Connexin Channels by Cyclodextrins J. Biol. Chem., May 28, 2004; 279(22): 22883 - 22892. [Abstract] [Full Text] [PDF]

				X. Lin and R. D. Veenstra Action potential modulation of connexin40 gap junctional conductance Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1726 - H1735. [Abstract] [Full Text] [PDF]

				A. P Moreno Biophysical properties of homomeric and heteromultimeric channels formed by cardiac connexins Cardiovasc Res, May 1, 2004; 62(2): 276 - 286. [Abstract] [Full Text] [PDF]