When Is a Potassium Channel Not a Potassium Channel?

Abstract

Ever since they were first observed in Purkinje fibers of the heart, funny channels have had close connections to potassium channels. Indeed, funny channels were initially thought to produce a potassium current in the heart called I _K2. However, funny channels are completely unlike potassium channels in ways that make their contributions to the physiology of cells unique. An important difference is the greater ability for sodium to permeate funny channels. Although it does not flow through the funny channel as easily as does potassium, sodium does permeate well enough to allow for depolarization of cells following a strong hyperpolarization. This is critical for the function of funny channels in places like the heart and brain. Computational analyses using recent structures of the funny channels have provided a possible mechanism for their unusual permeation properties.

Keywords: computer simulations; funny channel evolution; funny channel history; funny channel permeation; funny channels; hyperpolarization-activated channels; voltage-gated potassium channels.

Figure 1.

The structure of the pore region of funny channels and other channels containing the GY/FG triplet within the selectivity filter. (A) Amino acid sequence of the pore region in funny channels and other channels containing the GY/FG triplet. The selectivity filter amino acids are highlighted in yellow. The W434 residue of the Shaker channel and the equivalent residue in the other channels are shown in turquoise. The channels shown are the human SK potassium channel, the Shaker voltage-gated potassium channel from Drosophila melanogaster, the KcsA potassium channel from Streptomyces lividans, the KAT1 potassium channel from Arabadopsis thaliana, the human ether-a-go-go potassium channel, SthK, from Spirochaeta thermophila, SR HCN, the funny channel from the single-celled choanoflagellate Salpingoeca rossetta, SpHCN2, one of the funny channel isoforms found in the sea urchin Strongylocentrotus purpuratus, the human HCN1 channel, the human HCN2 channel, the human HCN3 channel, the human HCN4 channel, cHCNb channel from Ciona intestinalis, cHCNc channel from C. intestinalis, and cHCNb channel from C. intestinalis. (B) The solved structure of the pore region of the rabbit HCN4 channel (left; pdb # 7np4) and the SthK channel (right; pdb # 6cjq). Two of four subunits are shown. The regions shown for each subunit span the S5 and S6 transmembrane segments. The five amino acid residues of the selectivity filter and the first residue following the selectivity filter on the outer rim are shown in stick form and are identified by the letter next to it. (C) The solved structure of the pore region of the Shaker potassium channel (pdb # 7sj1) and the Shaker W434F potassium channel (pdb # 7sip) from D. melanogaster. Two of four subunits are shown. The regions shown for each subunit span the S5 and S6 transmembrane segments. The five amino acid residues of the selectivity filter and the first residue following the selectivity filter on the outer rim are shown in stick form and are identified by the letter next to it.