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- Leak channels; only for K : they are always open;
- Gated channels; these are channels with “gates“ (or locks) which are usually closed, but
can be opened by a stimulus when required:
• voltage gated: by a change in the electrochemical membrane potential;
• ligand gated: by a chemical stimulus, e.g. neurotransmitters (acetylcholine, dopa,
2+
glutamate, NO) or toxins (nicotine), or Ca
;
• stretch gated: by a mechanical stimulus, e.g. a physical change in the membrane as a
consequence of strain.

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The selectivity of ion channels for K and Na is
implemented by geometrical factors, as shown at the
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right hand side for a K selective channel: The Na
cation is too small to fit properly into the opening
provided by four oxygen functionalities of the channel.

Ionophores are macrocyclic compounds with mainly O-functional groups, which can
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form stable complexes in vivo specifically with Na or K . Models for ionophores are crown
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ethers, cryptands and calixarenes; Fig. 32. The selectivity for Na and K is determined by the
size (diameter) of the space available within the functionalities. Examples for naturally
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occurring ionophores are displayed in Fig. 33: Nonactin and enniatine (both for K ) und
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antamanide (for Na ). Antamanide is a cyclic decapeptide of composition -Val-Pro-Pro-Ala-
Phe-Phe-Pro-Pro-Phe-Phe-.

O O
O O
O O O O
O O O O O O
O
O O
15C5 18C6 Dibenzo-18C6
R

O O O O
OH
N N N N OH HO
O
O O R OH R
O O O O

R
C-221 C-222 Calix[4]aren

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Figure 32. Ionophore models suited for the coordination of Na and K : Crown ethers (top
row), cryptands (bottom left and centre), and a calixarene (bottom right). 18C6 = 18-crown-6
(18-membered ring, 6 O-functions); C221 = cryptand-221 (221 denotes the number of O-
functions in the three bridges between the amine-nitrogens). The symbol [4] in the calixarenes
indicated the number of phenolic units.