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Mechanisms of extracellular divalent and trivalent cation block of the sodium current in canine cardiac Purkinje cells.
Author(s) -
Sheets M F,
Hanck D A
Publication year - 1992
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1992.sp019265
Subject(s) - divalent , chemistry , purkinje fibers , sodium , gating , membrane potential , extracellular , voltage clamp , sodium channel , biophysics , ion , analytical chemistry (journal) , electrophysiology , inorganic chemistry , biochemistry , medicine , chromatography , organic chemistry , biology
1. Single canine cardiac Purkinje cells were internally perfused and voltage clamped with a large‐bore perfusion pipette for measurement of sodium ionic current (INa) in the absence and presence of extracellular group IIA divalent cations (Mg2+, Ba2+ and Ca2+), transition divalent cations (CO2+, Mn2+ and Ni2+), group IIB divalent cations (Cd2+ and Zn2+), and the trivalent cation La3+. 2. Open channel block of cardiac INa by external Ca2+, assessed from instantaneous INa‐voltage (I‐V) relationships, has been well described by a two‐barrier, one‐well model with a dissociation constant at 0 mV, KB(0), of 37 mM and an electrical distance, z' = delta, of 0.34. At the most negative test potentials there was less block of INa than predicted by the model, but correction of INa for the contribution of Na+ channel gating current (Ig) to the peak current improved the fit by the model. 3. The divalent cations Ba2+, Mg2+, CO2+ and Mn2+ produced voltage‐dependent, open channel block of INa, which by the two‐barrier, one‐well model predicted a similar z' about one‐third into the membrane field. The relative efficacy for voltage‐dependent block was CO2+ > Mn2+ > Ca2+ > Mg2+ > Ba2+ with respective KB(0)s of 11, 13, 37, 43 and 61 mM. 4. Cd2+, Zn2+ and La3+ produced block of INa at low concentrations that was nearly voltage independent with z' < or = 0.13. Fits of single‐site binding curves to peak INa in response to step depolarizations at positive test potentials gave the following apparent KD values: Zn2+ 0.14 mM, Cd2+ 0.27 mM and La3+ 0.50 mM. 5. In the presence of Cd2+, INa tail current relaxations were much faster than could be accounted for by Cd2+ binding to and/or screening of extracellular surface charges. Fits of the data to a model that assumed voltage‐dependent open channel block during the tail current relaxations estimated the KB(0) for Cd2+ to be 0.80 mM. 6. Both z' and KB(0) for Ni2+ from fits of the two‐barrier, one‐well model to instantaneous I‐V relationships varied as a function of [Ni2+], consistent with the hypothesis that Ni2+ blocked with similar affinity at a voltage‐dependent and a voltage‐independent site. At [Ni2+] > or = 5 mM, KB(0) was 7.6 mM and z' was 0.21.(ABSTRACT TRUNCATED AT 400 WORDS)