Tissue-specific effects of acetylcholine in the canine heart

Abstract

Acetylcholine (ACh) release from the vagus nerve slows heart rate and atrioventricular conduction. ACh stimulates a variety of receptors and channels, including an inward rectifying current [ACh-dependent K ϩ current (IK,ACh)]. The effect of ACh in the ventricle is still debated. We compared the effect of ACh on action potentials in canine atria, Purkinje, and ventricular tissue as well as on ionic currents in isolated cells. Action potentials were recorded from ventricular slices, Purkinje fibers, and arterially perfused atrial preparations. Whole cell currents were recorded under voltageclamp conditions, and unloaded cell shortening was determined on isolated cells. The effect of ACh (1-10 M) as well as ACh plus tertiapin, an IK,ACh-specific toxin, was tested. In atrial tissue, ACh hyperpolarized the membrane potential and shortened the action potential duration (APD). In Purkinje and ventricular tissues, no significant effect of ACh was observed. Addition of ACh to atrial cells activated a large inward rectifying current (from Ϫ3.5 Ϯ 0.7 to Ϫ23.7 Ϯ 4.7 pA/pF) that was abolished by tertiapin. This current was not observed in other cell types. A small inhibition of Ca 2ϩ current (ICa) was observed in the atria, endocardium, and epicardium after ACh. ICa inhibition increased at faster pacing rates. At a basic cycle length of 400 ms, ACh (1 M) reduced ICa to 68% of control. In conclusion, IK,ACh is highly expressed in atria and is negligible/absent in Purkinje, endocardial, and epicardial cells. In all cardiac tissues, ACh caused rate-dependent inhibition of ICa.

The Roles of Gβγ and Gα in Gating and Regulation of GIRK Channels

“…Heart expresses GIRK1 and GIRK4 in sinoatrial node, atrium, and Purkinje fibers, and much less in the ventricle (Beckmann et al, 2008;Calloe, Goodrow, Olesen, Antzelevitch, & Cordeiro, 2013;Gaborit et al, 2007;Karschin et al, 1994;Yamada et al, 1998). Nevertheless, GIRK1's RNA is as abundant as the major G protein-independent inward rectifier, IRK1 (Kir2.1) in the ventricle (Marionneau et al, 2005).…”

Vibrational Circular Dichroism and Theoretical Study of the Conformational Equilibrium in (−)‐S‐Nicotine

“…[3,4] However, nicotine also acts as a potent agonist of the nicotinic acetylcholine receptor (nAChR), [5,6] which is a key neurotransmitter of the central and peripheral nervous system, [7] and has an inhibitory effect in cardiac tissue resulting in heartrate lowering. [8] Nicotinic agonists and antagonists of nAChR have been identified as therapeutic targets for the treatment of numerous diseases including Parkinson's disease; Tourette's syndrome; anxiety, cognitive, and attention deficits; and smoke addiction. [5][6][7][8][9][10] Regarding the treatment of Parkinson's disease (PD), it has been demonstrated that nicotinic compounds provide an excellent alternative to l-DOPA therapy, [9] because the latter is well-known to cause dyskinesias.…”

Developmental changes in expression and biophysics of ion channels in the canine ventricle

“…I Ca was recorded as previously described with minor modifications [22]. The external solution contained (in mM): NaCl 140, CaCl 2 2.0, MgCl 2 1, glucose 10, HEPES 10, pH adjusted to 7.4 with NaOH.…”