Biomaterial Database

Modification of sodium channel inactivation by alpha-chymotrypsin in canine cardiac Purkinje cells. 1993

M F Sheets, and D A Hanck

Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.

BACKGROUND Studies of tetrodotoxin-sensitive sodium current (INa) after modification of inactivation by intracellular enzymes in mammalian cells have demonstrated a marked increase in peak INa at test potentials near current threshold causing a large, negative shift of the peak INa conductance-voltage relationship by approximately -20 mV. These findings support a kinetic model in which the unmodified Na channel has rapid and voltage-independent inactivation from the open state. However, the kinetics of cardiac Na channels differ from those of mammalian neuronal Na channels. In particular, inactivation of cardiac Na channels has been proposed to be more voltage dependent than that of tetrodotoxin-sensitive Na channels. To help understand the role of inactivation in cardiac Na channel kinetic behavior, we studied Na currents before and after modification of inactivation by the proteolytic enzyme, alpha-chymotrypsin. RESULTS Whole cell INa was measured in single canine cardiac Purkinje cells that were voltage clamped and internally perfused with a large-bore suction pipette. The decay of INa in response to step depolarizations was dramatically slowed after perfusion with intracellular alpha-chymotrypsin consistent with modification of inactivation. In contrast to mammalian tetrodotoxin-sensitive Na current, Boltzmann distribution fits to peak INa conductance-voltage (GNa-V) relationships after alpha-chymotrypsin showed no change in either the potential at half maximum conductance (V 1/2), after correction for the spontaneous background shift of INa kinetics, or in the voltage-dependence of conductance (i.e., slope factor of GNa-V relationships). Maximal peak INa conductance increased by 18%. INa tail-current relaxations at potentials < or = -110 mV, after correction for spontaneous shifts in Na channel kinetics, were also similar before and after modification by alpha-chymotrypsin. CONCLUSIONS alpha-chymotrypsin modified inactivation of cardiac INa with little or no change in activation, and cardiac Na channel inactivation was slow near threshold and played little role in determining V1/2 for peak INa conductance-voltage relationships.

UI	MeSH Term	Description	Entries
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D011689	Purkinje Cells	The output neurons of the cerebellar cortex.	Purkinje Cell,Purkinje Neuron,Purkyne Cell,Cell, Purkinje,Cell, Purkyne,Cells, Purkinje,Cells, Purkyne,Neuron, Purkinje,Neurons, Purkinje,Purkinje Neurons,Purkyne Cells
D002918	Chymotrypsin	A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.	Alpha-Chymotrypsin Choay,Alphacutanée,Avazyme
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013779	Tetrodotoxin	An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.	Fugu Toxin,Tarichatoxin,Tetradotoxin,Toxin, Fugu
D015222	Sodium Channels	Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.	Ion Channels, Sodium,Ion Channel, Sodium,Sodium Channel,Sodium Ion Channels,Channel, Sodium,Channel, Sodium Ion,Channels, Sodium,Channels, Sodium Ion,Sodium Ion Channel