Barium modulates the gating of batrachotoxin-treated Na+ channels in high ionic strength solutions.
Batrachotoxin-activated rat brain Na+ channels were reconstituted in neutral planar phospholipid bilayers in high ionic strength solutions (3 M NaCl). Under these conditions, diffuse surface charges present on the channel protein are screened. Nevertheless, the addition of extracellular and/or intracellular Ba2+ caused the following alterations in the gating of Na+ channels: (a) external (or internal) Ba2+ caused a depolarizing (or hyperpolarizing) voltage shift in the gating curve (open probability versus membrane potential curve) of the channels; (b) In the concentration range of 10-120 mM, extracellular Ba2+ caused a larger voltage shift in the gating curve of Na+ channels than intracellular Ba2+; (c) voltage shifts of the gating curve of Na+ channels as a function of external or internal Ba2+ were fitted with a simple binding isotherm with the following parameters: for internal Ba2+, delta V0.5,max (maximum voltage shift) = -11.5 mV, KD = 64.7 mM; for external Ba2+, delta V0.5,max = 13.5 mV, KD = 25.8 mM; (d) the change in the open probability of the channel caused by extracellular or intracellular Ba2+ is a consequence of alterations in both the opening and closing rate constants. Extracellular and intracellular divalent cations can modify the gating kinetics of Na+ channels by a specific modulatory effect that is independent of diffuse surface potentials. External or internal divalent cations probably bind to specific charges on the Na+ channel glycoprotein that modulate channel gating.
Cukierman
S
S
Department of Physiology, Loyola University Medical Center, Maywood, IL 60153.
D000818:Animals; D001464:Barium / Q000494:pharmacology*; D001496:Batrachotoxins / Q000494:pharmacology; D055592:Biophysical Phenomena; D001703:Biophysics; D001921:Brain / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D008051:Lipid Bilayers / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009994:Osmolar Concentration; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D012996:Solutions
D001496:Batrachotoxins; D008051:Lipid Bilayers; D015222:Sodium Channels; D012996:Solutions; D001464:Barium