Reversal Potential of the Calcium Current in Bull-frog Atrial Myocytes

1. Voltage clamp recordings of the calcium current (ICa) in single myocytes which were enzymatically isolated from bull-frog atrium show that a genuine reversal of the current flowing through Ca2+ channels can be recorded (ef. Reuter & Scholz, 1977; Lee & Tsien, 1982, 1984; Campbell, Giles & Shibata, 1988c). In normal 2.5 mM [Ca2+]0 Ringer solution this apparent reversal potential (Erev) is near +50 mV, a value well below the predicted thermodynamic Ca2+ equilibrium potential (ECa). 2. None the less, Erev shifts with variations in extracellular divalent ion concentrations (Ca2+, Sr2+ and Ba2+) according to the predictions of a Nernstian divalent cation electrode, i.e. approximately 29 mV per 10-fold change in the external concentration of divalent ion. 3. The existing theoretical analysis of this Erev has been extended in order to clarify its interpretation with regard to the selectivity characteristics of ICa. 4. The apparent reversal potential is analysed using a form of the constant field equation which has been modified to include (i) simultaneous monovalent and divalent cation movements and (ii) the presence of a surface potential (V'). This equation can be solved to yield an explicit expression for Erev. The effects of V' on apparent permeability ratios for the Ca2+ channel Erev are demonstrated. 5. In combination, our experimental results and calculations suggest that: (i) previous estimates of V' which were used to describe permeability (P) ratios of Ca2+ channels in various cardiac preparations may be in error, (ii) in normal [Ca2+]o the PNa/PCa ratio is very small, and (iii) PCa/PK must be greater than 1000. An analysis of the relative selectivity of the channel for divalent cations compared to K+ shows that PCa greater than PSr greater than PBa, assuming that PK remains the same after the divalent substitutions. 6. The Ca2+ channel in bull-frog atrial cells is thus much more selective for Ca2+ ions than had previously been estimated; in particular, inward flow of monovalent cations (e.g. Na+) through these channels does not contribute significantly to the observed ICa. The physiological implications of this high selectivity for Ca2+ ions are discussed.