Pharmacology

of
Action Potential

Mohanad AlBayati
Prof. Mohanad AbdulSattar Al-Bayati, BVM&S, MSc. Physiol.,
PhD. Pharmacology and Toxicology
College of Veterinary Medicine
University of Baghdad
Al Ameria, Baghdad
Phone: 0964 7700766650
E. Mail: aumnmumu@covm.uobaghdad.edu.iq
aumnmumu@yahoo.com
 Overview of Excitable cells

Nerve cells, muscle cells and several other cell types

are excitable, that is, they are activated by variations of
their membrane potentials.

Many of the macromolecules that…….

control cell excitation are

IMPORTANT DRUG TARGETS

 Clinical applications of drugs that influence
cell excitation
• blockade of nerve conduction for local anesthesia
• Reduction of nerve cell excitability in the brain in epilepsy
• Stabilization of mood in the treatment of bipolar disorder
• Reduction of vascular smooth muscle tone to reduce
blood pressure
• Suppression of aberrant excitation in cardiac arrhythmia

This list is not complete, but it suffices to illustrate

that the applications are important and diverse.
In order to understand how such drugs
work, we must first
understand cell excitation itself
Synaps
Other types of excitable cells
The two driving forces that generate diffusion
potentials across membranes
A diffusion potential arises if
(1) the membrane is selectively permeable for some
specific ion but not its counter ion, and
(2) there is a concentration gradient for the permeant ion.
Under these conditions, entropy will induce the permeant
ion to move downhill its concentration gradient, until the
ensuing charge imbalance creates an equally strong
Coulomb counterforce. This counterforce is reached at
the equilibrium potential, E0, which is determined by the
Nernst equation.
Equilibrium potentials for the major salt ions

Those of K+ and Cl− are negative, while the ones for Na+ and Ca++ are positive
Specific channels control ion permeabilities
Diffusion potentials with multiple ions: the
Goldman equation
Structure and function of voltage-gated
cation channels
Structure of a voltage-gated K+ channel
Structure of the K+ selectivity filter
Voltage-gated sodium channels sustain and
spread the action potential
Voltage-gated potassium channels extinguish
the action potential
Voltage-gated channels and action potentials
in the heart
 Drug effects on voltage-gated sodium (NaV)
channels

Sodium channels play a crucial role in the

propagation of action potentials, and thus
they are a good target when inhibition of
nerve conduction is desired, as it is in local
anesthesia. In addition, inhibitors of
sodium channels are also used in several
other situations that require neural
excitability to be dampened.
Fast and slow channel block
Diethylamine and phenol resemble parts of
the lidocaine molecule
Effects of diethylamine and of phenol on NaV
channel conductance
Drugs and poisons that act on NaV channels
Pharmacology of potassium channels
KATP channels regulate the tone of smooth
muscle cells
KATP channels in pancreatic β cells regulate
insulin secretion
Drugs that act on K+ channels
Pharmacology of calcium channels
Two calcium channels control the contraction
of striated muscle cells
 Entry of Ca++ through the DHPR is
necessary in the heart, but not in skeletal
muscle cells
Inhibitors of voltage-gated calcium channels
Structure of ω-conotoxin, an inhibitor of N-type
CaV channels
Agonists of transient receptor potential (TRP)
channels
Na+/K+-ATPase maintains the ion gradients
across the cytoplasmic membrane
Functional cycle of Na+/K+-ATPase
Na+/K+-ATPase activity as a function of KCl
and NaCl concentrations
 Effects of Rb+ and of Na+ on the
phosphorylation state of Na+/K+-ATPase
ATP is required to release Rb+ from tight
binding to Na+/K+-ATPase
Structures of the Na+/K+-ATPase inhibitors
ouabain and digitoxin
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