Effect of isoprenaline, carbachol, and Cs+ on Na+ activity and pacemaker potential in rabbit SA node cells.

Effects of isoprenaline, carbachol, and Cs+on intracellular Na+ activity ([Formula: see text]) and spontaneous action potentials were studied in multicellular and single cell preparations isolated from rabbit sinoatrial (SA) nodes.[Formula: see text] was measured with double-barreled Na+-selective microelectrodes and the fluorescent Na+-indicator sodium-binding benzofuran isophthalate (SBFI). In spontaneously beating cells,[Formula: see text] measured with Na+-selective microelectrodes and SBFI were 4.5 ± 1.2 mM (means ± SD, n = 21) in multicellular preparations and 4.0 ± 1.1 mM ( n = 16) in single cells, respectively. Measurements of[Formula: see text] with microelectrodes showed that isoprenaline increased[Formula: see text] from 4.7 ± 1.2 to 5.5 ± 1.6 mM ( n = 16, P < 0.01) and shortened the action potential cycle length (ACL) from 338 ± 46 to 269 ± 35 ms ( n = 16, P < 0.01). However, increasing the action potential rate by pacing produced a much smaller increase in[Formula: see text]. Changes in[Formula: see text] and ACL produced by isoprenaline were blocked by Cs+. The selective hyperpolarization-activated inward current ( I f) blocker ZD-7288 decreased [Formula: see text] from 5.2 ± 1.0 to 4.6 ± 1.3 mM ( n = 4, P < 0.01) and prolonged ACL from 394 ± 20 to 553 ± 68 ms ( n = 4, P < 0.01). The I f blocker substantially inhibited the increase in[Formula: see text] produced by isoprenaline. Carbachol and Cs+ decreased[Formula: see text] from 4.6 ± 1.4 to 3.9 ± 1.2 mM ( n = 15, P < 0.01) and from 4.9 ± 1.0 to 3.9 ± 1.3 mM ( n = 18, P < 0.01), respectively. In addition, carbachol and Cs+prolonged ACL from 345 ± 44 to 587 ± 100 ms ( n = 15, P < 0.01) and from 353 ± 30 to 464 ± 87 ms ( n = 18, P < 0.01), respectively. However, carbachol and Cs+ almost did not change [Formula: see text] when SA node cells became quiescent in a 25.4 mM extracellular K+ concentration. The results suggest that isoprenaline, ZD-7288, carbachol, or Cs+ might have changed[Formula: see text] and action potential rate by possibly stimulating or inhibiting I f carried by Na+. Measurements of[Formula: see text] with SBFI showed that isoprenaline, carbachol, and Cs+produced [Formula: see text] changes that were similar to those measured with the microelectrodes.