Mutant channels

Biophysical investigations of mutant Cavl.l channels in a variety of heterologous and native systems have also given varying results, some contradictory (Table 4). Although contested, a dominant theme appears to be a reduced current density and reduced rate of activation in mutant channels relative to wild-type (Sipos et al., 1995 Morrill and Cannon, 1999). Both effects are loss of function and could result in less calcium influx into the muscle cells during depolarizations. In... 

The frog oocytes expressing the mutant channels were studied using the patch-clamp method, which allows the characterization of single channels on intact cells. ... 

Gong Q, Keeney DR, Molinari M, Zhou Z. Degradation of trafficking-defective long QT syndrome type II mutant channels by the ubiquitin-proteasome pathway. J. Biol. Chem. 2005 280 19419-19425. 

B) A mutant channel lacking residues 6 tfirougfi 46 does not inactivate. (C) Inactivation can be restored by adding a peptide consisting of residues I through 20 at a concentration of 100 (xM. [After... 

The experimental results shown in Figure 7-38 demonstrate that inactivation of channels depends on the ball domains, occurs after channel opening, and does not require the ball domains to be covalently linked to the channel protein. In other experiments, mutant channels lacking portions of the 40-residue chain connecting the ball to the SI helix were expressed in frog oocytes. Patch-clamp measurements of channel activity showed that the shorter the chain. 

A EXPERIMENTAL FIGURE 7-38 Experiments with a mutant channel lacking the N-terminai giobular domains support the ball-and-chain inactivation modei. The wild-type Shaker channel and a mutant form lacking the amino acids composing the N-terminal ball were expressed in Xenopus oocytes. The activity of the channels then was monitored by the patch-clamp technique. When patches were depolarized from -0 to -1-30 mV, the wild-type channel opened for =5 ms and then closed (red curve), whereas the mutant channel opened normally, but could not close (green curve). When a chemically synthesized ball peptide was added to the cytosolic face of the patch, the mutant channel opened normally and then closed (blue curve). This demonstrated that the added peptide inactivated the channel after it opened and that the ball does not have to be tethered to the protein in order to function. [From W. N. Zagotta et al., 1990, Science 250 568.]... 

Fig. 3.1-8 The activity of an exogenenous nimodipine, the endogenous, wild-type L-type calcium channel was dissected using channel (blue) is blocked and the activity of a mutation that effects nimodipine the mutant channel (green) is revealed,...

Voltage-dependent channels close by a process called "inactivation," rapidly after opening. In drosophila mutant channels, the cytoplasmic amino terminus in its own channel forms the inactivation gate. The central... 

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