Do potassium channel blockers affect the resting membrane potential?

Question

I am reading about scorpion venoms and toxins for my bio class and they appear to have a variety of potassium channel blockers. My professor asked "What effect would this have on a neuron?" and naturally two things came to mind

1. Potassium channels are necessary for repolarization
2. Potassium channels participate in controlling the concentration gradient of the cell.

I have found evidence in articles supporting the first claim, but I don't know much about the second.

Do potassium channel blockers affect the resting membrane potential? Would they significantly alter the concentration gradient?

Answer 1

2. Potassium channels participate in controlling the concentration gradient of the cell.

I would rephrase this to "Sodium/potassium pumps establish the concentration gradients of sodium and potassium across the cell membrane." Potassium channels do not.

I have found evidence in articles supporting the first claim, but I don't know much about the second.

Right; because the channels don't set up concentration gradients.

Do potassium channel blockers affect the resting membrane potential?

If they block the resting state "leak" potassium channels, you bet. The resting membrane potential is largely set by the electrical conductance through those channels. Blocking them would greatly depolarize the cell compared to typical resting membrane potential values. But there are many different potassium channels. You may be thinking of blocking the delayed rectifier potassium channel, which shouldn't do much at all to change the resting membrane potential.

Would they significantly alter the concentration gradient?

Probably not, since though the cell would be losing less potassium through this conductance, what matters more to the concentration gradient of potassium are the sodium/potassium pumps.

Answer 2

Short answer
Scorpion venom mostly affects neuronal firing activity by inhibiting recovery.

Background
There are some 100 subtypes of K⁺ channels and some 120 different scorpion toxins known. Of this host of toxins, the majority were tested on Shaker-related channels (subfamily KV1.x). Some peptides were shown to act on the Ca²⁺-activated K⁺ channels (KCa1.1, KCa3.1, KCa2.x. The family of so-called g-KTx toxins is specific for the ether-a-go-go family of K⁺ channels (KV11.x) (Rodriguez de la Vega & Possani, 2004).

The Shaker subfamily and the ether-a-go-go family are all voltage-gated channels and hence closely involved in action potential generation (Coleman et al., 1999; Shepard et al., 2007)]; the Ca²⁺-activated K⁺ channels are activated when Ca²⁺ enters the cell, which is an event typically associated with action potentials too.

Hence, based on this information I conclude that scorpion venom mainly blocks the repolarization phase of neurons, meaning the maximum firing rate will be drastically reduced because recovery is blocked. Neurons can fire, but they will not be able to recover from continuous firing.

Scorpion venom is not strongly associated with potassium leak channels (KCNK family). Although other families may also affect the resting membrane potential, it is the KNCK family that is mostly associated with generating the cell resting membrane potential (Cohen et al., 2009). hence, scorpion venom will not affect the resting membrane potential too much.

References
- Coleman et al., J Neurochem (1999); 73: 849–58
- Rodriguez de la Vega & Possani, Toxicon (2004); 43: 865–875
- Shepard et al., Schizophrenia Bulletin; 33(6): 1263–9
- Cohen et al., Eur Biophys J (2009); 39(1): 61-73