Acid-sensing ion channels (ASICs) constitute a branch of the super-gene family of amiloride-sensitive sodium channels. So far five different ASICs have been cloned from mammalian tissues. They are activated by a drop of extracellular pH but differ with respect to effective agonist concentration, desensitization and mRNA expression pattern. Here we report cloning of ASIC4, a new protein showing about 45% identity to other ASICs. ASIC4 is 97% identical between rat and human and shows strongest expression in pituitary gland. Moreover, we detected expression throughout the brain, in spinal cord, and inner ear. ASIC4 cannot be activated by a drop of extracellular pH in Xenopus oocytes, suggesting association with other subunits or activation by a ligand different from protons. Our results suggest a role for ASICs also in endocrine glands.
The kinetic behaviour and functional role of potassium ion (K+) channels mediating a fast-inactivating K+ current (IK(A)) has been widely discussed. Activating in the subthreshold range of excitation, IK(A) channels are assumed to reduce the excitatory effect of depolarizing membrane currents in a time-dependent manner. Here we report that IK(A) channels not only open in response to a depolarization but open again after repolarization of the membrane. Although the current in response to the depolarization is rapidly inactivating, the current elicited by repolarization declines slowly and produces long-lasting afterhyperpolarizations under current-clamp conditions. This implies an additional physiological role for IK(A) channels, particularly those that activate positive to the threshold of excitation. The underlying biophysical mechanism was studied by fast-application of peptides corresponding to the N-terminal end of the IK(A) channel proteins. It was found to be a voltage-dependent release of the inactivation gate.
Myoballs were cultured from biopsies of adult human skeletal muscle without the use of antimitotic drugs. The sodium currents flowing during stepwise depolarization of the myoball membrane were investigated with the wholecell recording technique. The temperature range covered 10-37 degrees C. Two types of sodium channel were distinguished by their different sensitivity to tetrodotoxin (TTX). The channel with normal TTX sensitivity seemed identical with the sodium channel in adult muscle, the channel with less TTX sensitivity seemed identical with the juvenile channel found in developing and in denervated muscle. The activation and inactivation parameters of both channel types were quantitatively determined. The activation parameters of the two channel types were identical, but in comparison to the h infinity-curve of the adult sodium channels the h infinity-curve of the juvenile channels was positioned at more negative potentials, had a less steep slope, and when the temperature was decreased, its point of inflection shifted more in negative direction.
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