THE concentration of cytoplasmic free calcium (Ca) ion regulates a variety of cellular processes1–4, including hormone secretion, histamine secretion, neurotransmitter release, mitosis and muscle contraction. For some of these processes the activating signal is a rapid influx of Ca ions across the plasma membrane during an action potential. One way of controlling the magnitude of such processes would be a regulation of the amount of Ca influx during each action potential. A mechanism capable of this type of control has recently been ascribed to the Ca conductance system of molluscan neurones. It is called ‘Ca facilitation’, and is an increase in the inward Ca current (ICa) observed when a test voltage-clamp pulse is preceded by a depolarised, conditioning prepulse5–8. Ca facilitation could cause an enhanced Ca influx during a repetitive train of action potentials. An opposing process, Ca inactivation, has also been described in excitable tissue9–13. Ca inactivation, like Na inactivation, is a decrease in inward current caused by a depolarising prepulse. Thus, facilitation would cause an increase and inactivation a decrease in ICa during repetitive voltage-clamp pulses. Facilitation of ICa has not been observed directly under voltage-clamp because inward ICa is usually accompanied by a large, outward K current (IK) (ref. 14). We have eliminated IK by using a new technique to replace intracellular potassium with caesium, and report here that ICa inactivates without evidence of facilitation.
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