UNASSIGNED: @entity299 slowing produced by cardiac parasympathetic (vagal) stimulation is thought to be the result of modulation of the @entity934 -activated @entity3529 current (IK,ACh) and the pacemaker current (If) in sinoatrial (SAN) pacemaker cells. However, the contribution of these and other ion currents to @entity73 is controversial. Here, we examined the contributions of IK,ACh and If to @entity73 in 15 isolated, vagal-innervated preparations of @entity840 atria, using 300nM @entity13472 (TQ) and 2 M @entity22724 to obtain full and substantial block of these currents, respectively. Blocking IK,ACh alone reduced atrial rate responses to 10-s trains of regular vagal stimulation (supramaximal stimulation, 2-ms duration, 1-10Hz) by ~50% (P<0.01; N=11); blocking If alone had no effect (N=7). Blocking both IK,ACh and If produced ~90% reduction (P<0.01; N=4). Atrial cycle length response to a single burst of vagal stimuli (3 stimuli at 50Hz), delivered at the optimum phase of the cycle was strongly suppressed by blocking IK,ACh (reduced by 98%; P<0.01; N=9), and modestly reduced by blocking If alone (by ~43%; P=0.20; N=6). The response was abolished by combined block of IK,ACh and If (P=0.04; N=4). Our data show that modulation of IK,ACh and If is sufficient to account for all the @entity73 observed in this preparation. The vagally-induced negative shift in activation potential for If will be opposed by hyperpolarisation of SAN through activation of IK,ACh. Thus removal of IK,ACh by TQ may have exaggerated the overall contribution of If to @entity73 .

Effects of tertiapin-Q and XXXX on changes in sinoatrial pacemaker rhythm during vagal stimulation.

@entity3529 :: ('D011188', 'Chemical') :: ['K(+)'] @entity13472 :: ('MESH:C029738', 'Chemical') :: ['tertiapin-Q'] @entity73 :: ('MESH:D003072', 'Disease') :: ['vagal slowing'] @entity840 :: ('10141', 'Species') :: ['guinea-pig'] @entity22724 :: ('MESH:C082246', 'Chemical') :: ['ZD7288'] @entity299 :: ('MESH:D006331', 'Disease') :: ['Heart rate'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity22724 :: (MESH:C082246,Chemical) :: ['ZD7288']
