Abstract
Physiologists have long known that ions play a central role in the excitability of nerve and muscle. In a series of papers between 1881 and 1887, Sidney Ringer showed that the solution perfusing a frog heart must contain salts of sodium, potassium, and calcium mixed in a definite proportion if the heart is to continue beating (Hille, 1992). Later, Hodgkin and Huxley, in their classical studies on squid giant axons (Hodgkin and Huxley, 1952;a,Hodgkin and Huxley, 1952;b), found that the conductance changes of membranes could be separated into two distinct “permeation” pathways, one for sodium and another for potassium. This early recognition that distinct proteins conferred selective passageways for different ions was fully established with the discovery and use of pharmacological agents and toxins. For example, the toxins tetrodotoxin (TTX) and saxitoxin (STX) selectively and reversibly block Na+ current without affecting K+ conductance (Hille, 1966; Hille, 1968; Nakamura et al., 1965). These early studies laid the foundation for the concept of channel “gating,” wherein the availability of the channel’s active site or pore is allosterically regulated in a time- and voltage-dependent manner (Hodgkin and Huxley, 1952c).
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Cho, HC., Backx, P.H. (2001). Three-Dimensional Structure of the K+Channel Pore: Basis for Ion Selectivity and Permeability. In: Archer, S.L., Rusch, N.J. (eds) Potassium Channels in Cardiovascular Biology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1303-2_2
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