PT  - JOURNAL ARTICLE
AU  - Yao, J A
AU  - Saxena, N C
AU  - Ziai, M R
AU  - Ling, S
AU  - Tseng, G N
TI  - Effects of n-dodecylguanidine on A-type potassium channels: role of external surface charges in channel gating.
DP  - 1995 Jul 01
TA  - Molecular Pharmacology
PG  - 160--171
VI  - 48
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/48/1/160.short
4100  - http://molpharm.aspetjournals.org/content/48/1/160.full
SO  - Mol Pharmacol1995 Jul 01; 48
AB  - n-Dodecylguanidine (C12-G) is an amphipathic compound with a guanidine moiety, which is positively charged at physiological pH, and a hydrophobic side chain. Its effects on an A-type K+ channel clone (rKv1.4) expressed in Xenopus oocytes were examined. C12-G caused a concentration-dependent (1-20 microM) positive shift in the voltage dependences of the following channel properties: activation, inactivation, rate of decay during depolarization, and rate of recovery from inactivation. C12-G was effective when added to the bath solution but was without effect when applied to the cytoplasm of oocytes, indicating an extracellular site of action. The effects of C12-G were antagonized by elevation of the extracellular Mg2+ concentration and by external guanidine ions but were augmented by lowering of the ionic strength of the external solution. C12-G did not affect the instantaneous current-voltage relationship for rKv1.4 or the time constant of decay during strong depolarizations, when the voltage dependence of channel activation approached a plateau. Our observations suggest that C12-G exerts its actions by causing a positive shift in the external surface potential around rKv1.4, without altering the ion permeation process or voltage-independent transition steps. In canine ventricular myocytes, C12-G caused changes in the function of a native A-type K+ channel similar to those seen with rKv1.4. However, C12-G had negligible effects on the voltage dependence of the slow delayed-rectifier K+ channel in the same cell type, suggesting that the actions of C12-G are not nonspecific.