Effects of n-dodecylguanidine on A-type potassium channels: role of external surface charges in channel gating.
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.
Yao
J A
JA
Department of Pharmacology, Columbia University, New York, New York 10032, USA.
Saxena
N C
NC
Ziai
M R
MR
Ling
S
S
Tseng
G N
GN
D000818:Animals; D002413:Cations, Divalent; D004285:Dogs; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D051665:Kv1.4 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D014981:Xenopus
D002413:Cations, Divalent; D006146:Guanidines; D051665:Kv1.4 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C006921:dodine; D019791:Guanidine