Some effects of short-chain phospholipids and n-alkanes on a transient potassium current (I A ) in identified Helix neurons

Many effects of short-chain phospholipids and n-alkanes on the squid axon sodium current (I_Na) are consistent with mechanisms involving changes in membrane thickness. Here, we suggest that the actions of short-chain phospholipids on an A-type potassium current (I_A) in two-microelectrode voltage clamped Helix D1 and F77 neurons are incompatible with such simple mechanisms. Diheptanoyl phosphatidylcholine (diC₇PC, 0.2 and 0.3 mm) caused substantial (58 and 79%), and in some cases partially reversible, increases in I_A amplitude. These were correlated with hyperpolarizing shifts of up to –7 mV in the voltage dependence of current activation. The voltage dependence of steady-state inactivation was also moved in the hyperpolarizing direction. These effects are the opposite of those described for squid I_Na. 0.5 Saturated n-pentane and saturated n-hexane caused significant (–3 and –6 mV) hyperpolarizing shifts in the voltage dependence of I_A inactivation, qualitatively consistent with their effects on squid I_Na, while the voltage dependence of activation was moved slightly to the left or unchanged. Hydrocarbons had variable effects on peak current amplitude, although saturated n-pentane produced a clear suppression. DiC₇PC caused a 25% increase in the time constant of macroscopic I_A inactivation (_b) but 0.5 saturated n-pentane and saturated n-hexane reduced _b by 40%. The effects of these agents on current-clamped cells were broadly consistent with their opposing actions on _b—phospholipids tended to reduce excitability and n-alkanes tended to increase it. Possible mechanisms of I_A perturbation are discussed.We gratefully acknowledge financial support from the Science and Engineering Research Council and the Wellcome Trust. We would also like to thank Prof. H. Meves, Dr. N. Franks and Dr. W. Lieb for helpful discussions.