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 inactivat ed by extracellular calcium (Ca-o(2+)) in Xenopus oocytes has been stu died using the voltage-clamp technique. 2. The reversal potential of t he 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, determ ined during either voltage ramps of 0.5 s duration or at steady state, displayed pronounced rectification at both hyperpolarized and depolar ized potentials. However, instantaneous I-V relations showed less rect ification and could be fitted by the constant field equation assuming the above K+:Na+:Cl- permeability ratios. 4. Ion substitution experime nts indicated that relatively large organic monovalent cations and ani ons 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), flufena mic 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 reversa l potential. 6. Preinjection of oocytes with antisense oligonucleotide against connexin 38, the Xenopus hemi-gap-junctional protein, inhibit ed I-c ,by 80% without affecting its ion selectivity, thus confirming and extending the recent suggestion of Ebihara that I-c, represents cu rrent 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 develo pmental downregulation of I-c, minimizes any toxic effect I-c, activat ion 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 othe r Ca-o(2+)-inactivated conductances seen in a wide variety of cell typ es and which have previously been interpreted as arising either from C a-o(2+)-masked channels or from changes in the ion selectivity of volt age-gated Ca2+ or K+ channels.