Selective inhibition of the transmembrane Ca conductivity of mammalian myocardial fibres by Ni, Co and Mn ions

Summary

According to earlier studies on mammalian papillary muscles, Ni and Co ions reduce the Ca dependent mechanical response whilst the action potential persists. In order to clarify the mode of action of these cations together with those of Mn their effects on the transmembrane fast Na and of the slow Ca currents were studied in voltage clamp experiments using the double sucrose gap technique. By a conditioning clamping procedure the Ca current was separated from the Na current. The following results were obtained:

• 1. Ni ions (2 mM) and Co ions (2 mM) strongly depress the Ca conductivity of the membrane. The same blockade was observed under the influence of Mn ions (2 mM). Even in the continued presence of Ni, Co or Mn the transmembrane Ca conductivity can be restored to a varying degree by increasing the extracellular Ca concentration.

• 2. In contrast to this strong inhibitory effect on the transmembrane Ca inward movements the fast transient Na current is only slightly affected if at all.

• 3. Apart from their selective inhibitory action on the transmembrane Ca current, Co ions show some additional features a) enhancement of its inhibitory action by repeated membrane depolarizations. b) Co-induced replacement of the slow Ca inward current by a transitory fast inward current component, c) synergetic effects of Co with Ca in restricting the fast Na current.

• 4. The selective inhibition of the transmembrane Ca conductivity clearly demonstrates the existence of a separate channel for Ca which is independent from the fast Na channel of the membrane.

This dual membrane transport system allows the regulation of the Ca dependent process of excitation-contraction coupling independently of a simultaneous influence on excitation.