Inactivation without facilitation of calcium conductance in caesium-loaded neurones of Aplysia

Abstract

THE concentration of cytoplasmic free calcium (Ca) ion regulates a variety of cellular processes^1–4, 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 (I_Ca) observed when a test voltage-clamp pulse is preceded by a depolarised, conditioning prepulse^5–8. 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 tissue^9–13. 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 I_Ca during repetitive voltage-clamp pulses. Facilitation of I_Ca has not been observed directly under voltage-clamp because inward I_Ca is usually accompanied by a large, outward K current (I_K) (ref. 14). We have eliminated I_K by using a new technique to replace intracellular potassium with caesium, and report here that I_Ca inactivates without evidence of facilitation.