High selectivity of the i f channel to Na+ and K+ in rabbit isolated sinoatrial node cells

The ionic selectivity of the hyperpolarizationactivated inward current (i_f) channel to monovalent cations was investigated in single isolated sinoatrial node cells of the rabbit using the whole-cell patch-clamp technique. With a 140 mM K⁺ pipette, replacement of 90% external Na⁺ by Li⁺ caused a –24.5 mV shift of the fully activated current/voltage I/V curve without a significant decrease of the slope conductance. With a 140 mM Cs⁺ pipette, the i_f current decreased almost proportionally to the decrease in external [Na⁺]_o as Li⁺ was substituted. These responses are practically the same as those observed with N-methyl glucamine (NMG⁺) substitution, suggesting that the relative permeability of Li⁺ compared with Na⁺ for the i_f channel is as low as that of NMG⁺. When Cs⁺ or Rb⁺ was substituted for internal K⁺, the fully activated I/V relationship for i_f showed strong inward rectification with a positive reversal potential, indicating low permeability of the i_f channel for Cs⁺ and Rb⁺. These results show that the i_f channel is highly selective for Na⁺ and K⁺ and will not pass the similar ions Li⁺ and Rb⁺. Such a high degree of selectivity is unique and may imply that the structure of the i_f channel differs greatly from that of other Na⁺ and K⁺ conducting channels.