Effects of manganese and other agents on the calcium uptake that follows depolarization of squid axons

1. The Ca‐sensitive photoprotein aequorin was injected into squid axons and the light response to stimulation or depolarizing voltage clamp pulses recorded. 2. The effects of Mn 2+ , Co 2+ , Ni 2+ , La 3+ and of the organic Ca antagonists D‐600 and iproveratril on the early tetrodotoxin‐sensitive and late tetrodotoxin‐insensitive components of the light response were studied. 3. The late tetrodotoxin‐insensitive component can be blocked, reversibly, by concentrations of Mn, Co and Ni that reduce but do not block the tetrodotoxin‐sensitive component. The late component can also be blocked by La 3+ and the organic Ca antagonists D‐600 and iproveratril. 4. Mn 2+ , Co 2+ , Ni 2+ and the drug D‐600 all reduce the Na currents, but have little effect on either outward or inward K currents. Tetraethylammonium blocks the outward K current but has no appreciable effect on the tetrodotoxin‐insensitive entry of Ca. 5. Concentrations of Mn between 5 and 50 m M substantially reduce the light output during a train of action potentials; they also slightly reduce the rate of rise of the action potential. 6. On pharmacological grounds it is concluded that the tetrodotoxin‐insensitive component of Ca entry does not represent Ca ions passing through the K permeability channels. There must exist a potential‐dependent late Ca channel that is distinct from the well known Na and K channels of the action potential. A possible function for this late Ca channel in the coupling of excitation to secretion is discussed.