Channel conductance, potential dependence

Verapamil (Class IV antiarrhythmic drug) is an effective agent for atrial or supraventricular tachycardia. A Ca++ channel blocker, it is most potent in tissues where the action potentials depend on calcium currents, including slow-response tissues such as the SA node and the AV node. The effects of verapamil include a decrease in heart rate and in conduction velocity of the electrical impulse through the AV node. The resulting increase in duration of the AV nodal delay, which is illustrated by a lengthening of the PR segment in the ECG, reduces the number of impulses permitted to penetrate to the ventricles to cause contraction. 

Nelson I would like to return to what David Eisner mentioned about the plasma membrane determining the steady-state free Ca2+, and what Rick Paul said about sparks and long-conductance Ca2+-dependent K+ (BK) channels. We have looked at cerebral arteries from PLB knockout mice. The spark frequency and the associated transient BK current frequency are elevated by about a factor of three. SR load goes up, the membrane potential hyperpolarizes and the artery relaxes. It would be useful to measure membrane potential under all the conditions as well as determine the voltage dependence of tone, to make sure that your manipulations are not simply changing the membrane potential. 

Electrical measurements with purified, reconstituted Na+ channels have demonstrated that an individual channel can exist in either conductive or nonconductive states. As shown in figure SI.4, the fraction of time that a channel spends in the conductive state depends strongly on Ai//, increasing abruptly as A iff is made less negative. These results agree well with the notion that a local depolarization of the plasma membrane switches the nearby Na+ channels to their conductive states and thus launches an action potential that propagates down the cell. 

There is much more awareness of the possible effect of the electric fields normal to the plane of the membrane on the structure and on the function of membrane proteins. However, no such relation was experimentally documented. There is an appreciable amount of information on the potential dependence of channel conductance, which is assumed to be caused by shifts of charged groups within the channel (41). These shifts correspond to small changes in conformation that could not be detected by methods sensitive to the secondary structure of the proteins. In the present and in some previous reports (7, 8), we have shown that membrane potentials of comparable magnitude to the physiological membrane potentials are sufficient to modulate the secondary structure of membrane proteins. The effect may be direct or indirect. The indirect effect shifts part of the molecular fraction immersed... 

The molecular mechanism operative in the change in ion channel conductances is not yet clearly understood. However, it is likely that these ion channels are composed of lipid-protein complexes. There are at least two theories for the opening of the sodium channel (1) Voltage-dependent ion channel conductance When the depolarization potential is greater than the threshold value, the sodium channel opens. (2) Ca " removal from the membrane outer surface (probably, from the outer part of the sodium channel) Such removal acts as a trigger for opening the sodium channel. It seems... 

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