Anomalous permeation of Na+ through a putative K+ channel in rat superior cervical ganglion neurones.
1. An unanticipated inward tail current was recorded from freshly isolated adult rat superior cervical ganglion (SCG) neurones using the whole-cell variant of the patch-clamp technique. The tail current was present when Na+ was substituted for tetraethylammonium (TEA) as the primary monovalent cation in external solutions designed to isolate Ca2+ channel currents (0.5 microM tetrodotoxin present and K+ omitted). 2. The tail current was observed following step potentials positive to -30 mV and reached half-activation near -9.0 mV. The decay of the tail current was voltage dependent and could be described with two time constants. Between potentials of -120 and -70 mV, tau f, the fast component, varied from 3 to 8 ms and tau s, the slow component, changed from 12 to 30 ms, respectively. 3. The tail current was not carried by Ca2+, and did not appear to flow through a voltage-gated Ca2+ channel or a Ca(2+)-dependent channel as it persisted in the absence of external Ca2+ or in the presence of the Ca2+ channel blocker, Cd2+ (0.1 mM). 4. Varying the external [Cl-] did not alter the reversal potential of the tail current indicating that Cl- was not the charge carrier. 5. The reversal potential of the tail current changed in accordance with the Nernst relationship when [Na+]i/[Na]o was altered. Our results suggested that this 'unusual or unanticipated current' (Iu) was carried primarily by Na+. 6. Iu was inhibited by the K+ channel-blocking agents quinidine (0.1 mM), external Ba2+ (5 mM) and internal Cs+ (145 mM). TEA (20 mM either internally or externally) and dendrotoxin (10 microM) were not effective inhibitors of Iu. 7. The decay time constants of the tail current and parameters of activation and inactivation of Iu were similar to those of TEA-insensitive delayed rectifier-type K+ channel currents observed in the presence of 145 mM external K+. 8. Iu was reduced in the presence of either external or internal K+. The interaction of external K+ with Na+ on the Iu tail amplitude was reminiscent of anomalous mole-fraction behaviour. 9. Ion permeability studies revealed that the channel producing Iu had a permeability sequence to monovalent cations of 3.5:2.5:2:1:0.5 for Rb+, K+, Cs+, Na+ and Li+, respectively. 10. These data suggest that in the absence of external K+, the ion selectivity of a TEA-insensitive K+ channel in sympathetic neurones is profoundly diminished. Under these conditions, Na+ traversing a K+ channel can generate an unanticipated inward current.(ABSTRACT TRUNCATED AT 400 WORDS)
Zhu
Y
Y
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2300.
Ikeda
S R
SR
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010539:Permeability; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000378:metabolism*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015220:Calcium Channels; D002712:Chlorides; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D012964:Sodium; D011188:Potassium