On the kinetics of the potassium channel activated by acetylcholine in the S-A node of the rabbit heart

Abstract

1. Voltage-clamp experiments were conducted on small specimens of rabbit sinoatrial node. In the same preparation the dose-response curve of the potassium current induced by application of different concentrations of acetylcholine (ACh), the time constant of relaxation and the current fluctuations were measured. From these measurements the apparent dissociation constant and the rate constants for the opening and closing of the ACh-activated potassium channel were estimated. 2. In the presence of neostigmine a measurable response was recorded at around 10(-8) M ACh, the saturation was reached at 10(-4) M, and the half saturation was attained at around 10(-6) M. 3. The time constant of relaxation at --35 mV decreased from 100 ms at 10(-8) M to 45 ms at 10(-4) M ACh. 4. The variance of the fluctuations of the ACh-activated current increased with increasing ACh concentration to a peak value of around 10(-5) M. 5. From the above 3 kinds of measurements, opening and closing rate constants of about 12s-1 and 10s-1, respectively, and a dissociation constant of 1.7 microM were calculated. 6. The Katz-Miledi model was considered to be appropriate to describe the reaction of ACh with the muscarinic receptor in the S-A node. 7. The current on ionophoretic application of ACh was computed using the rate constants and taking into account diffusion in the S-A node in which the density of receptors is low. The computed response had a similar time course to the recorded current.

Disparities in voltage-sensor charge and electromotility imply slow chloride-driven state transitions in the solute carrier SLC26a5

“…In subsequent model renditions we intend to evaluate this possibility, and the possible effects of electric field on anion binding. In its present form, however, our simple model derives from typical ligand gated channels (e.g., ACh receptor channels) where fast ligand-binding kinetics leads to very much slower conformational changes that gate open conductance (46,47). For prestin, the slower, voltage-independent intermediate conformational change enables voltage sensing.…”

Reconstruction of sino-atrial node pacemaker potential based on the voltage clamp experiments.

“…Recently,the kinetic property of the ACh-induced K current(iAch)was examined in the rabbit S-A node cell (NOMA and TRAUTWEIN,1978;NOMA et al, 1979a,b;OSTERRIEDER et al,1980).According to these studies,the opening where A is the concentration of ACh.The amplitude of iAch under full activation is, Using these equations the ACh-induced current was incorporated in the present model.In the computation in Fig.7-2,it was assumed that 3 concentrations of The present study using the Hodgkin-Huxley type model elucidated the major role of is in generating both the action potential and the pacemaker depolarization.This model well simulated the electrical responses of the S-A node cell to various experimental conditions.…”

Mathematical model of the changes in heart rate elicited by vagal stimulation.

“…We used a Hodgkin-Huxley type mathematical model to predict the changes in SCL elicited by ACh (Figure l).i ? - 9 Briefly, the time change in membrane potential (V) is given by dV/dt=-(l/C)I T (4) where C is the membrane capacitance and I T is the sum of six membrane ionic currents: I Nl +, a fast Na + current; I s , the slow inward current; I h , a hyperpolarization-activated current; I K +, a K + current; I L , a leakage current; and IK A O,, the AChactivated K + current. I nin ,= (I T -Iic Aai )-Each of the six ionic currents is a nonlinear function of V and the six ionic gates, which are solutions to a coupled system of seven nonlinear ordinary differential equations.…”