The electrophysiological and pharmacological properties of cardiac myocytes from the hearts of adult transgenic mice engineered to overexpress nerve growth factor (NGF) in the heart were studied.

There was a 12 % increase in the ventricular myocyte capacitance in NGF myocytes consistent with cardiac hypertrophy, and action potential duration at 90 % repolarization (APD₉₀) was prolonged by 142 % compared with wild‐type (WT) myocytes. This was due, at least in part, to a decrease in the density of two K⁺ currents, I_to and I_K(ur), which were significantly reduced in NGF mice with no change in their electrophysiological characteristics. We found no change in the current density or electrophysiological properties of the L‐type Ca²⁺ current.

The effect on I_to and I_K(ur) of TEA and 4‐aminopyridine (4‐AP) was not different in cells isolated from WT and NGF mice. The prolongation of APD observed in NGF cells was mimicked in WT cells by exposure to 1 mm 4‐AP, which partially blocked I_to, completely blocked I_K(ur) and increased APD₉₀ by 157 %.

The isoprenaline‐induced increase in I_Ca was significantly smaller in NGF myocytes than in WT myocytes. This was not due to a decrease in β‐adrenergic receptor (β‐AR) density, as this was increased in NGF tissue by 55 %. Analysis of β‐AR subtypes showed that this increase was entirely due to an increase in β₂‐AR density with no change in β₁‐ARs.

The response of the β‐AR‐coupled adenylyl cyclase system to isoprenaline, Gpp(NH)p and forskolin was studied by measuring cAMP production. In NGF tissue, isoprenaline elicited a significantly smaller response than in WT myoyctes and this was not due to reduced adenylyl cyclase activity as the responses of NGF tissue to guanylylimidodiphosphate (Gpp(NH)p) and forskolin were unaffected.

In conclusion, the overexpression of NGF in the mouse heart resulted in a decrease in the current density of two K⁺ channels, which contributed to the prolongation of the cardiac action potential. Despite an increase in β₂‐AR density in the hearts of the NGF mice, the response to isoprenaline was diminished, and this was due to an uncoupling of the β‐ARs from the intracellular signalling cascade. These potentially pathological changes may be involved in the occurrence of ventricular arrhythmias in cardiac hypertrophy and failure, and this mouse provides a novel model in which to study such changes.