CONTRIBUTION OF NA+ CA2+ EXCHANGE TO ACTION-POTENTIAL OF HUMAN ATRIALMYOCYTES/

The Ca2+ dye indo 1 was used to record internal Ca2+ (Ca-i) transients in order to investigate the role of the Na+/Ca2+ exchange current (I- Na/Ca) in whole cell patch-clamped human atrial myocytes. After the ac tivation of the L-type Ca2+ current by test pulses (20 ms) at +20 mV, a tail current (I-tail) was activated at a holding potential of -80 mV with a density of -1.29 +/- 0.06 pA/pF. The time course of I-tail fol lowed that of Ca-i transients. I-tail was suppressed by dialyzing cell s with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraaceti c acid, applying 5 mM caffeine, or substituting external Na+ with Li+, indicating that this current was mainly generated by I-Na/Ca. Two typ es of action potential were recorded: type A, which is characterized b y a narrow early plateau followed by a late low plateau phase, and typ e B, which is characterized by a small initial peak followed by a prol onged high plateau phase. Type B action potentials were found in large r cells than type A. action potentials (membrane capacitance 81.8 +/- 4.5 and 122.4 +/- 7.0 pF in types A and B, respectively, P < 0.001). S ubstitution of external Na+ with Li+ shortened the late plateau of the type A action potential and the prolonged plateau of the type B actio n potential. Suppression of Ca-i transients by caffeine shortens the l ate part of both types of action potentials, whereas its lengthening e ffect on the initial phase of action potentials can result from severa l different mechanisms. The beat-to-beat dependent relationship betwee n Ca-i transients and action potentials could be mediated by I-Na/Ca. Delayed afterdepolarizations were present in a significant proportion of atrial myocytes in our experimental conditions. They were reversibl y suppressed by Li+ substitution for Na+, suggesting that they are gen erated by I-Na/Ca. We conclude that I-Na/Ca plays a major role in the development of action potentials and delayed afterdepolarizations in i solated human atrial myocytes.