The ion selectivity of a membrane conductance inactivated by extracellular calcium in Xenopus oocytes

1. The ion selectivity of a membrane ion conductance that is inactivated by extracellular calcium (Ca-o(2+)) in Xenopus oocytes has been studied using the voltage-clamp technique. 2. The reversal potential of the Ca-o(2+)-sensitive current (I-c) was measured using voltage ramps (-80 to +40 mV) as a function of the external concentration (12-240 mM) Of NaCl or KCl. The direction and amplitude of the shifts in reversal potentials are consistent with permeability ratios of 1 : 0.99 : 0.24 for K+ : Na+ : Cl-. 3. Current-voltage (I-V) relations of I-c, determined during either voltage ramps of 0.5 s duration or at steady state, displayed pronounced rectification at both hyperpolarized and depolarized potentials. However, instantaneous I-V relations showed less rectification and could be fitted by the constant field equation assuming the above K+:Na+:Cl- permeability ratios. 4. Ion substitution experiments indicated that relatively large organic monovalent cations and anions are permeant through I-c, channels with the permeability ratios K+ : NMDG(+): TEA(+) : TPA(+) : TBA(+) : Gluc(-) = 1 :0.45:0.35:0.2:0.2: 0.2. 5. External amiloride (200 mu M), gentamicin (220 mu M), flufenamic acid (40 mu M), niflumic acid (100 mu M), Gd3+ (0.3 mu M) or Ca2+ (200 mu M) caused reversible block of I-c without changing its reversal potential. 6. Preinjection of oocytes with antisense oligonucleotide against connexin 38, the Xenopus hemi-gap-junctional protein, inhibited I-c ,by 80% without affecting its ion selectivity, thus confirming and extending the recent suggestion of Ebihara that I-c, represents current carried through hemi-gap-junctional channels. 7. In vitro and in vivo maturation of oocytes resulted in a significant decrease in I-c, conductance to 7% and 2% of control values, respectively. This developmental downregulation of I-c, minimizes any toxic effect I-c, activation would have when the mature egg is released into Ca-o(2+)-free pond water. 8. The results of this study are discussed in relation to other Ca-o(2+)-inactivated conductances seen in a wide variety of cell types and which have previously been interpreted as arising either from Ca-o(2+)-masked channels or from changes in the ion selectivity of voltage-gated Ca2+ or K+ channels.