Effects of ACh and adenosine mediated by Kir3.1 and Kir3.4 on ferret ventricular cells

Abstract

The inotropic effects of ACh and adenosine on ferret ventricular cells were investigated with the action potential-clamp technique. Under current clamp, both agonists resulted in action potential shortening and a decrease in contraction. Under action potential clamp, both agonists failed to decrease contraction substantially. In the absence of agonist, application of the short action potential waveform (recorded previously in the presence of agonist) also resulted in a decrease in contraction. Under action potential clamp, application of ACh resulted in a Ba2+-sensitive outward current with the characteristics of muscarinic K+ current ( I K,ACh); the presence of the muscarinic K+ channel was confirmed by PCR and immunocytochemistry. In the absence of agonist, on application of the short ACh action potential waveform, the decrease in contraction was accompanied by loss of the inward Na+/Ca2+exchange current ( I NaCa). ACh also inhibited the background inward K+ current ( I K,1). It is concluded that ACh activates I K,ACh, inhibits I K,1, and indirectly inhibits I NaCa; this results in action potential shortening, decrease in contraction, and, as a result of the inhibition of I K,1, minimum decrease in excitability.

ACh-induced depolarization in inner ear artery is generated by activation of a TRP-like non-selective cation conductance and inactivation of a potassium conductance

“…Several reports demonstrated that muscarinic stimulation inhibits inward rectifier K + -channels, e.g., in rat locus coeruleus neurons (Shen et al, 1992), in cardiac muscle cells (Dobrzynski et al, 2002) and in rat prefrontal cortex pyramidal neurons (Carr et al, 2007). Shen & North (Shen et al, 1992) presented a mathematical model of the two conductance alterations, activation of a cation conductance and inactivation of an inward rectifier K + -conductance, for the muscarine-induced depolarization in the neurons.…”

Identification of GIRK2-4 subunits in human esophageal smooth muscle cells

“…Under physiological ionic conditions, the muscarinic receptor-mediated current is carried with a reversal potential between -10 and 0 mV, whereby depolarization is produced; thus, the discharge of action and slow-wave potentials initiates or accelerates unless the depolarization is extremely strong (31,32). Previous studies have shown that ACh activates and modulates the activity of GIRK channels in esophageal SMCs (33,34).…”

From Action Potential-Clamp to "Onion-Peeling" Technique – Recording of Ionic Currents Under Physiological Conditions

“…Even in the case when agonist/antagonist affects only one population of receptors, signal transduction pathways often couple to more than one ionic current; AP-clamp is uniquely suited for studying the drug concentration-dependent effects on multiple currents. As example, the frequency-dependent effects of isoproterenol on I Ca,L , I Ks , and I Cl in guinea pig ventricular cells (Rocchetti et al, 2006) and the effects of acetylcholine and adenosine on I K1 in ferret cardiac myocytes (Dobrzynski et al, 2002) were clarified using the AP-clamp technique.…”