CONTRIBUTION OF ATP-SENSITIVE POTASSIUM CHANNELS TO THE ELECTROPHYSIOLOGICAL EFFECTS OF ADENOSINE IN GUINEA-PIG ATRIAL CELLS

1. Adenosine caused dose-dependent action potential abbreviation in mu lticellular guinea-pig atrial preparations, an action antagonized by g lyburide (IC50, 31 mu M) in both physiological and low-chloride superf usate. 2. When 5 mM ATP was included in pipettes for whole-cell voltag e clamp of isolated guineapig atrial myocytes, adenosine (10 mu M) inc reased the holding current at -40 mV from 41 +/- 8 to 246 +/- 31 pA (m ean +/- S.E.M., P < 0.01), and glyburide (20 mu M) returned the holdin g current to 69 +/- 11 pA (P < 0.01 vs. adenosine alone). Acetylcholin e (10 mu M) also increased the holding current, but its effects were n ot altered by glyburide. 3. Both adenosine and acetylcholine induced a n additional current component in response to 500 ms voltage steps. Gl yburide partially inhibited the adenosine-induced current, but did not alter the effect of acetylcholine. In the presence of maximally effec tive acetylcholine concentrations, adenosine increased membrane conduc tance (P < 0.01), although to a lesser extent than in the absence of a cetylcholine. 4. Single K+ channel activity was seen in only one of ei ght cell-attached patches in the absence of adenosine or acetylcholine (0.5 mM Ba2+ in bath and pipette solutions). With acetylcholine (10 m u M) in the pipette, inwardly rectifying channels (conductance, 41 +/- 5 pS) were seen in five of six patches. With adenosine (10 mu M) in t he pipette, single-channel activity was seen in twelve of fourteen pat ches with two populations of channels, one similar to that induced by acetylcholine and another higher-conductance channel (72 +/- 5 pS) tha t showed less inward rectification. Glyburide (20 mu M) suppressed the high-conductance channel (68 +/- 2 pS) leaving a single channel type with a conductance of 36 +/- 5 pS and strong inward rectification. 5. We conclude that K-ATP(+) channels contribute to the electrophysiologi cal actions of adenosine on guinea-pig atrium in the presence of physi ological intracellular ATP levels, and may therefore play a role in th e cardiac electrophysiological effects of adenosine in the absence of myocardial ischaemia.