The influence of charge on the effects of n-octyl derivatives on sodium current inactivation in rat sensory neurones.
1. The whole-cell patch-clamp technique was used to determine the actions of n-octyl sulphate (OS-) anions and n-octyl trimethylammonium (OTMA+) cations on sodium current steady-state inactivation and peak amplitude in cells isolated from dorsal root ganglia of neonatal rats and maintained in short-term tissue culture. This paper concentrates on the effects of external addition but the actions of internal OS- and OTMA+ are briefly considered. 2. The main action of external OS- was to cause a hyperpolarizing shift in the voltage dependence of the steady-state inactivation parameter, h infinity. At 1-6 mM OS- caused a shift in the mid-point of the h infinity curve of around -30 mV. The shape of the h infinity curve was altered in a concentration-dependent manner. Internal OS- had no discernible effect on the shape or position of the h infinity curve. 3. External OS- produced a relatively small (less than 25%) reduction in the maximum current achieved following pre-pulses sufficiently negative to remove resting steady-state inactivation. 4. By contrast, external OTMA+ had little effect on the voltage dependence of h infinity and produced a small, but significant, increase in the maximum sodium current. 2 mM-external OTMA+ moved the mid-point of the h infinity curve (Vh) 5 mV in the depolarizing direction (relative to the mean of control and reversal curves) and increased the maximum current by 13%. One millimolar internal OTMA+ induced a frequency-dependent current block. 5. Raising the external calcium concentration from 2 to 20 mM (in the presence of 2 mM-magnesium and 5 mM-cobalt) caused an 18 mV depolarizing shift in Vh, consistent with a reduction in the negativity of an external surface charge. The maximum current was reduced by 22%. 6. One millimolar OS- reduced the surface potential of egg phosphatidylcholine (EPC) monolayers (at an air-0.5 M-NaCl interface) by 35 mV but 1 or 2 mM-OTMA+ produced only a 2-3 mV increase. The quantitative agreement between the effects of OS-, on Vh in the rat and on monolayer surface potential, decreased with increasing concentration.(ABSTRACT TRUNCATED AT 400 WORDS)
Elliott
A A
AA
Department of Anatomy and Physiology, The University, Dundee.
Elliott
J R
JR
D000476:Alkanesulfonates / Q000494:pharmacology*; D017738:Alkanesulfonic Acids; D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*
D000476:Alkanesulfonates; D017738:Alkanesulfonic Acids; D000644:Quaternary Ammonium Compounds; C042006:octyltrimethylammonium; D012964:Sodium; C042005:1-octanesulfonic acid; D002118:Calcium