Premium
Modification of Sodium Channel Inactivation by α‐chymotrypsin in Canine Cardiac Purkinje Cells
Author(s) -
SHEETS MICHAEL F.,
HANCK DOROTby A.
Publication year - 1993
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.1993.tb01254.x
Subject(s) - conductance , biophysics , sodium channel , purkinje fibers , sodium , intracellular , chymotrypsin , electrophysiology , chemistry , medicine , biochemistry , enzyme , biology , trypsin , physics , organic chemistry , condensed matter physics
Modification of Cardiac I Na by α‐chymotrypsin. Introduction: Studies of tetrodotoxinsensitivc sodium current (I Na ) after modification of inactivation by intracellular enzymes in mammalian cells have demonstrated a markid increase in peak I Na at test potentials near current threshold causing a large, negative shift of the peak I Na 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 nenronal 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 hehavior, we studied Na currents before and after modification of inactivution by the proteolytic enzyme, α‐chymotrypsin. Methods and Results: Whole cell I Na was measured in single canine cardiac Purkinje cells that were voltage clamped and internally perfused with a large‐bore suction pipette. The decay of I Na in response to step depolarizations was dramatically slowed after perfusion with intracellular α‐chyniotrypsin consistent with modification of inactivation. In contrast to mammalian tetrodotoxin‐sen‐sitive Na current, Boltzmann distribution fits to peak I Na conductance‐voltage (G Na ‐V) relationships after α‐chymotrypsin showed no change in either the potential at half maximum conductance (V 1/2 ), after correction for the spontaneous background shift of I Na kinetics, or in the voltage‐dependence of conductance (i.e., slope factor of G Na ‐V relationships). Maximal peak I Na conductance increased by 18%. I Na tail‐current relaxations at potentials ≤−110 mV, after correction for spontaneous shifts in Na channel kinetics, were also similar before and after modification by α‐chymotrypsin. Conclusion: α‐chymotrypsin modified inactivation of cardiac I Na with little or no change in activation, and cardiac Na channel inactivation was slow near threshold and played little role in determining V 1/2 for peak I Na conductance‐voltage relationships.