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Na+ currents through low‐voltage‐activated Ca2+ channels of chick sensory neurones: block by external Ca2+ and Mg2+.
Author(s) -
Lux H D,
Carbone E,
Zucker H
Publication year - 1990
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.1990.sp018287
Subject(s) - chemistry , membrane potential , dorsal root ganglion , sodium , analytical chemistry (journal) , reversal potential , ion , hyperpolarization (physics) , biophysics , patch clamp , stereochemistry , anatomy , dorsum , biochemistry , chromatography , receptor , nuclear magnetic resonance spectroscopy , biology , organic chemistry
1. Whole‐cell currents through low‐voltage‐activated (LVA) Ca2+ channels carried by monovalent cations were studied in chick dorsal root ganglion (DRG) cells. 2. With 120 mM [Na+] on both sides of the membrane and [Ca2+]o less than or equal to 100 microM, the currents reversed at 0 mV. Their half‐times of activation and inactivation were strictly voltage‐dependent and decreased to near‐constant values of 0.6‐0.85 and 40 ms, respectively, at positive membrane potentials. The longer activation times were observed with [Ca2+]o greater than or equal to 50 microM. 3. The selectivity of the Ca2+ channel for monovalent ions with reference to internal Na+ was evaluated from the reversal potential. The Li+ and Na+ permeabilities were similar. The permeability ratios of K+ and Rb+ were 0.45, and 0.33 for Cs+. 4. Micromolar increases in [Ca2+]o produced small voltage shifts of half‐times of activation (less than or equal to +3 mV at 10 microM and +10 mV at 500 microM), but strongly depressed the Na+ current. The Ca2(+)‐induced block of Na+ current satisfied a 1:1 stoichiometry with an apparent KD of 1.8 microM at ‐20 mV. The block was, however, relieved with more positive and negative potentials, with KDs of 55 and 8.5 microM at +90 and ‐110 mV, respectively. 5. Relaxation time constants of block and unblock of Na+ currents through the LVA Ca2+ channel were measured on step changes to and from membrane potentials at which pronounced Ca2(+)‐induced block occurred. 6. At ‐20 mV, the time constants of block decreased with micromolar increase in [Ca2+]o in line with a blocking rate coefficient of 1.9 x 10(8) M‐1 s‐1, but settled to values of 0.18 ms at [Ca2+]o beyond 50 microM. The Na+ currents were unblocked with time constant (tau u) of around 0.25 ms at strongly positive and negative membrane potentials at 22 degrees C. 7. Tau u failed to show any obvious dependence on [Ca2+]o up to the millimolar range. This finding contradicts suggestions that removal of the block occurs in a [Ca2+]o‐dependent manner as a result of an increased probability of Ca2+ ion mobilization by repulsive forces with increased Ca2+ occupation of the channel. 8. The time course of unblock of Na+ currents was strongly temperature‐dependent showing a Q10 of 2.5 for tau u. 9. The voltage dependence of the Na+ current block by Ca2+ ions is best accounted for by a single, centrally located Ca2+ binding site.(ABSTRACT TRUNCATED AT 400 WORDS)